Pharmacological Properties History

Psychostimulants are a broad family of drugs that include compounds from naturally occurring plant alkaloids (e.g., caffeine, cocaine, ephedrine, nicotine) to synthetic amphetamine derivatives such as D-amphetamine, methamphetamine, and 3,4-methylenedioxymetham-phetamine ( MDMA ecstasy) as well as methylpheni-date. Some of these psychostimulants are available over-the-counter (e.g., caffeine) or under prescription for a given medical indication (e.g., methylphenidate), while others are illicit...

M1 Muscarinic Receptor Preferring Drugs

There has been considerable effort in the development of pharmacological agents that selectively act at the M1 muscarinic acetylcholine receptor, in particular M1 mus-carinic agonists. This is, in large part, because of studies indicating that M1 muscarinic acetylcholine receptors are altered in Alzheimer's disease and schizophrenia (Langmead et al. 2008). Both of these conditions are marked by cognitive deficits and thus there has been an Muscarinic Cholinergic Receptor Agonists and...

Role of Pharmacotherapy

Physical Withdrawal Treatment General Pharmacological Withdrawal Strategies In the majority of cases, treatment of patients suffering from alcoholism starts with the termination of alcohol use and treatment of withdrawal symptoms. The general consensus is that the complicated alcohol withdrawal syndrome (severe physical withdrawal or withdrawal with seizures, alcohol hallucinosis or delirium tremens) requires pharmacological treatment. It is also agreed that adequate hydration, electrolyte...

Impact of Psychoactive Drugs

Many behavioral procedures have been used to assess the effect of psychoactive drugs on ethanol preference in nonhumans (Egli 2005). The most common approach is to assess ethanol intake relative to the intake of an alternative fluid (e.g., water) in a procedure that allows the animal to orally self-administer both fluids at the same time. For example, many studies have offered rats and mice a choice between drinking tubes containing 10 ethanol versus water in the home cage. Other studies have...

Pharmacological Modulation

The effects of a variety of pharmacological challenges on attentional bias have been studied. Firstly, administration of small to moderate doses of alcohol seems to increase attentional bias for alcohol- and smoking-related cues in heavy drinkers and tobacco smokers, respectively (see Field and Cox 2008). Alcohol affects a variety of neuro-transmitter systems, but its direct effects are to increase GABA activity and reduce glutamate activity, which then has knock-on effects on other...

Gaba

Absence epilepsy J uptake epilepsy, epileptic syndromes, and alcoholism GABA-T modifications DP + anxiety and panic disorders SZ J PBR DP PBR GABA and Peripheral Benzodiazepine Receptors Platelets express GABA transporters and the uptake of this amino acid has been reported disrupted in patients affected by absence epilepsy, although the functional impact of the antiepileptic drugs taken by the patients has not been completely clarified. Also GABA transaminase (GABA-T) has been studied, mainly...

Zuclopenthixol

Zuclopenthixol is a multi-receptor blocking thiox-anthene antipsychotic of the first generation. Its plasma half-life amounts to 12-28 h and it is mainly metabolized by 2D6 CYP450 isoenzymes. It is also available in a short-acting intramuscular depot preparation that has an elimination half-life of 48-72 h. IT T First-Generation Antipsychotics Zopiclone is a non-benzodiazepine sedative-hypnotic acting as an agonist at the benzodiazepine binding site on Consolidated List of Psychoactive...

Predictive Validity for Antidepressant Treatments

The FST and TST demonstrate good predictive validity for measuring the effects in animals of drugs that are used clinically to treat depression. Antidepressant drugs produce various pharmacological effects on diverse neu-rotransmitters and have been divided into different structural classes. All clinically effective antidepressant treatments produce reductions of immobility, including tricyclics, monoamine oxidase inhibitors, SSRIs, and atypical antidepressants. In addition, somatic treatments...

Breakpoint Synonyms

Breakpoint is used as a dependent variable in experiments using a progressive ratio (PR) schedule of reinforcement. A breakpoint is said to have been reached when the response output falls below a predefined level. In self-administration experiments, the breakpoint is often defined as the final ratio in effect (i.e., response requirement) when the last injection was delivered. Alternatively, the breakpoint can be defined as the total number of reinforcing events during the session.

Current Concepts and State of Knowledge

Apoptosis may be triggered by signals from within the cell or proximal and distal cells, as well as exogenous agents apoptotic cell death may also result from the withdrawal of trophic factors ( nerve growth factors). All of these triggers initiate a cascade of events that results in the elimination of cells without releasing harmful substances into the surrounding areas. Apoptosis is not associated with an inflammatory response in situ, apoptotic cells are phagocytosed by macrophages or...

G

Responded to at least two previous treatments and who remain troubled by severe and impairing anxiety symptoms (Baldwin et al. 2005 Tyrer and Baldwin 2006). Only few randomized controlled trials (RCTs) have allowed the assessment of the relative efficacy of different drugs, when compared with placebo. A recent analysis of RCT findings found an overall mean effect size of 0.39, with pregabalin having the highest effect (0.50) and the azapirone anxiolytic buspirone the lowest effect (0.17)...

N

NRT nicotine replacement therapy ADHD attention-deficit hyperactivity disorder AD Alzheimer's disease Nicotinic Agonists and Antagonists. Fig. 4. Schematic overview of the predominant central nAChR subtypes that are targets for the treatment of the central nervous system (CNS) disorders discussed in this chapter. Examples of CNS areas that are modulated by nAChRs are cortex (CTX), prefrontal cortex (PFC), hippocampus (HIPP), thalamus (THAL), locus coeruleus (LC), ventral tegmental area (VTA),...

S

Memory, as they typically can affect other forms of learning independent of the hippocampus. As such, preclinical tests of spatial learning in rodents, either in intact animals or those subjected to treatments that impair spatial learning, are often used as an initial assay to investigate the effects of potential cognition enhancing drugs. Drugs with interference from glutamatergic transmission, particularly those which block the n-methyl-D-aspartate (NMDA) receptor subtype, severely interfere...

Iu

AUzbay and Kayaalp 1995 1000.7 kcal L aUzbay and Kayaalp 1995 1000.7 kcal L liquid diet as a vehicle for alcohol administration. Above 10 g kg day alcohol consumption for a couple of week and more than 150 mg dl blood ethanol concentrations may be adequate for development of physical dependence on alcohol in rats (Uzbay and Kayaalp 1995). It has been recommended that in an acceptable liquid diet 36-50 of total energy should be acquired by ethanol (Lieber and DeCarli 1989 Uzbay and Kayaalp...

Sympathectomy Definition

Lesion of the sympathetic (noradrenergic) branch of the peripheral autonomic nervous system. Experimental Neuronal plasticity Short-term plasticity Definition In general terms, synaptic plasticity describes a change, persistent or transient, of morphology, composition, or signal transduction efficiency at a neuronal synapse in response to intrinsic or extrinsic signals. Long-term potentiation (LTP) and long-term depression (LTD) likely represent the most extensively studied forms of synaptic...

Specificity of Drug Action

Although there are tentative neuroendocrine mechanisms to account for overeating and increased body weight following the administration of different psychotropic drugs, what is missing in relation to most of the agents we have discussed is a clear description of more fundamental psychological behavioral factors that might contribute to weight gain. For example, it is likely that (in addition to any specific action on appetite control processes or energy balance), sedative effects of...

Early Ventral Hippocampal Lesion Model

An animal model in which the ventral hippocampal region in rats is lesioned using an excitotoxic agent. This lesion is performed at an early age (typically postnatal day 7). These animals develop several schizophrenialike phenomena in adulthood. Interestingly, most of the symptoms occur after puberty in accordance with the clinical literature on schizophrenia. Schizophrenia Animal Models Feeding can be defined as the behavioral response necessary for replenishing energy substrates to maintain...

Definition

The class of sleep disorders known as Parasomnias (L. Para next to Somnus sleep) includes some of the most unusual, challenging, fascinating, and potentially instructive of all behavioral disorders. These are clinical disorders characterized by abnormal behavioral or physiological events, usually unpleasant or undesirable, which accompany sleep-specific sleep stages or sleep wake transitions (American Academy of Sleep Medicine 2005 American Psychiatric Association 2000 see Table 1). Parasomnias...

M4 Muscarinic Receptor Preferring Drugs

The M4 muscarinic acetylcholine receptor is another mus-carinic acetylcholine receptor subtype in which there is significant interest in developing selective agents to generate novel treatments for both schizophrenia and Parkinson's disease. Despite interest in the M4 musca-rinic acetylcholine receptor, there are a relative lack of compounds that are highly selective for this muscarinic receptor subtype. Comparable to developing new targets for the M1 muscarinic receptor, the development of...

Dissociative Anesthetics

Anthony Absalom1, David Menon2 department of Anesthesiology, University Medical Centre Groningen, Groningen, Nehterlands 2University Division of Anesthesia, Addenbrooke's Hospital, Cambridge, UK Dissociative anesthesia is a form of anesthesia characterized by catalepsy, catatonia, analgesia, and amnesia. It does not necessarily involve loss of consciousness, and thus does not always imply a state of general anesthesia. Dissociative anesthetics probably produce this state by interfering with the...

Fyx

Produced by drugs and concluded that a simple process of conditioned aversion could not account for all of the findings. A variation of a one-taste model where preferences do emerge involves drug taste preference conditioning (see Alcohol Preference Tests). In the case of morphine taste preference conditioning, the development of a preference for the solution containing morphine can be made apparent against a baseline comprising a normal rejection of the aversive solution of morphine in...

Obsessive Compulsive Anxiety Disorders

Fineberg1'2, Ashwini Padhi1'3 department of Psychiatry, Queen Elizabeth II Hospital, Hertfordshire Partnership NHS Foundation Trust, Welwyn Garden City, Hertfordshire, UK 2Postgraduate Medical School, University of Hertfordshire, Hatfield, UK Hertfordshire Partnership NHS Foundation, Community Mental Health Team, Edinburgh House, St. Albans, Hertfordshire, UK Obsessive-compulsive disorder (OCD) is a common, debilitating illness that was considered untreatable until the 1960s. Since...

Tricyclic Antidepressants TCAs

Several TCAs are considered to be selective NRIs, including nortriptyline, lofepramine with its active metabolite desipramine, protriptyline, and the tetracyclic agent maprotiline (Preskorn 2009). TCAs were developed from phenothiazines to be used as possible sedatives, anti-histamines, analgesics, and antiparkinsonian drugs in the 1950s (Brunton et al. 2006). Imipramine, the first TCA developed, was tested in 500 patients with various psychiatric disorders. Of the patients who were tried on...

Mechanisms of Action

There are four known NT receptors (Kinkead and Nemeroff 2006 for review). The NT1 and NT2 receptors are G protein-coupled with the classic seven transmem-brane-spanning regions. NT2 is a receptor with low affinity for NT that also binds the histamine H1 receptor antagonist levocabastine. The NT1 receptor is a levocabas-tine-insensitive receptor with high affinity for NT. Two other identified receptors, NT3 (sortilin) and NT4 (SorLA LR11) are members of the family of Vps10p domain receptors with...

Perfusion Fluids

One of the crucial aspects in microdialysis studies is that the composition of the perfusion medium must be physiological, i.e., isotonic with respect to that of the interstitial space. However, several fluids are being used currently that differ in their electrolytic composition concentration (reviewed by Benveniste and Huttemeier 1990). With little variation, the fluids used to perfuse dialysis probes are those derived from Krebs-Ringer solutions or artificial CSF. Typically, the...

Extending the Paradigm The Pluridimensional Nature of Drug Efficacy

The discovery and acceptance of inverse agonism as a widespread phenomenon in the mode of action of many drugs has led to additional studies on the molecular nature of drug efficacy and its manifestations. There are now numerous examples where the same ligand, acting at the same receptor, can display totally different degrees of efficacy, ranging from positive to inverse, depending on the cellular background and or the signal pathway being measured. For example, propranolol is an inverse...

Chronic Disappointment Reaction Synonyms

A syndrome involving lowered or dysphoric mood that occurs in response to a perceived unpleasant situation or set of experiences that is repetitive or enduring. The offending experience typically represents an assault on the individual's self-concept or self-esteem. The person experiencing a chronic disappointment reaction may feel overmatched by the circumstances and may feel helpless and or hopeless in terms of prospects for improving the situation. Such a person may engage in any of a number...

Wjv

In moderate doses, it is used to reduce physical fatigue, to prevent drowsiness and sleep, and to maintain and restore mental alertness and wakefulness. However, at higher doses, these stimulatory effects can become excessive and lead to an unpleasant and dysphoric physical and mental state that is labeled caffeinism and is also known colloquially as coffee nerves'' or caffeine jitters.'' The common symptoms of caffeinism are essentially exaggerations of the effects...

Info

Fluoxetine, Paroxetine, Venlafaxine, Reboxetine (Likely to produce minor or moderate adverse effects) Desipramine, Imipramine, Clomipramine, Nortriptyline, Citalopram, Sertraline, Fluvoxamine, Escitalopram, Nefazodone, Moclobemide (Likely to produce severe effects or presumed to be potentially dangerous) Flurazepam, Nitrazepam, Flunitrazepam, Estazolam, Triazolam, Lormetazepam, Temazepam, Midazolam, Brotizolam, Quazepam, Loprazolam, Zopiclone Diazepam, Chlordiazepoxide, Oxazepam, Lorazepam,...

Plw

Seizures) and electroconvulsive shock (ECT). Amphetamine was first synthesized in 1927 but its use was confined to the treatment of narcolepsy. It was noted that amphetamine was ineffective in the treatment of major depression As is apparent from this group of drugs, until the latter part of the twentieth century the psychoactive drugs that were available to the psychiatrist were extremely limited and mainly used to calm or sedate disturbed patients. The Revolution in Pharmacopsychiatry There...

Dysthymic Disorder

Department of Psychiatry, Columbia University, New York, NY, USA Chronic low-grade depression Dysthymia Neurotic Depression Dysthymic disorder is a mood disorder that is characterized by chronic mild depression. To meet DSM-IV criteria of dysthymic disorder, an individual must have depressed mood for most of the day, for more days than not'' for at least 2 years. In addition, there must be two or more of the following symptoms poor appetite or overeating insomnia or hypersomnia low energy or...

Methylphenidate

MPH is available in immediate release formulation (IR-MPH), in different extended release forms (ER-MPH), and as dexmethylphenidate (DMPH, the active d-isomer of MPH), which is also marketed in both immediate and extended release forms. The short-term efficacy of MPH for treating ADHD has been conclusively demonstrated by showing significant improvements on standardized rating scales, such as the Conners Global Index, the Con-ners Inattention Hyperactivity with Aggression subscale, or the...

Action Potentials Synonyms

Nerve impulse Nerve spikes Definition Action potentials are pulse-like waves traveling along excitable membranes. Action potential initiation occurs when the voltage of the membrane increases sufficiently (depolarizes), thus activating (opening) voltage-gated sodium channels. Since the concentration of sodium channels outside the cell is much larger than the inside, sodium ions rush into the cell and represent the fast upstroke portion of the action potential wave. The Na channels close as the...

Psychoactive Drugs that Modulate HPA Axis Reactivity

First, almost all drugs that change central neuronal processes initially modulate basal and stress-induced HPA axis activity, because they acutely change homeostasis (Table 1). Here, drugs that affect parts of the regulatory mechanisms of the HPA axis and that are used in clinical practice are described. Benzodiazepines. Benzodiazepines are a major first line of treatment in anxiety disorders. However, little is known of their effect on HPA axis reactivity in man. Administrations of 1 mg...

Receptors

The actions of the various HPA axis hormones are mediated by receptors. CRF has a high affinity to the CRF-1 receptors and a lower affinity to the CRF-2 receptors, which have actually their own privileged ligands urocortin II and III. CRF-1 receptors are on pituitary corticotrophs and have a discrete localization in limbic-midbrain circuitry such as e.g., in the amygdala, where CRF promotes emotional arousal. Activation of the CRF-2 receptor ligands produces complimentary responses. There is...

Cachexia

Cachexia is a wasting syndrome involving reduced appetite, loss of body weight, and muscle atrophy. In contrast to other causes of weight loss such as anorexia nervosa or dieting, weight loss due to cachexia is involuntary. Individuals with cachexia are not actively attempt to lose weight. These symptoms are commonly observed in cancer patients undergoing chemotherapy treatment. Eating Disorder Anorexia Nervosa Micaela Morelli1'2'3, Nicola Simola1 department of Toxicology, University of...

Taste Reactivity Test

Tardive dyskinesia (TD) is a chronic neuromotor side effect of dopamine-blocking medications, characterized by abnormal involuntary movements of voluntary musculature that are generally slow and that can be irreversible. It can include abnormal rotatory or sinuous movements of the mouth, lips, neck, trunk, hands, arms, and legs. It is identified as a side effect of long-term antipsychotic use risk factors have been identified (e.g., age, duration of exposure), but there is no specific means of...

GABA and the Inhibitory Interneuron Clocking Networks

Complex brains have developed specialized mechanisms for the grouping ofprincipal cells into temporal coalitions of local or distant networks, the inhibitory interneuron clocking networks. They consist of GABAergic inter-neurons of rich diversity. In cortical circuits, these neurons control spike timing of the principal cells, sculpt neuronal rhythms, select cell assemblies, and implement brain states (Klausberger and Somogyi 2008). To achieve this regulatory control, distinct GABAergic...

Opioids

Morgan2 1Brain & Mind Research Institute M02G, The University of Sydney, Sydney, NSW, Australia 2Department of Psychology, Washington State University Vancouver, Vancouver, WA, USA The term opiate refers to drugs extracted from opium, i.e., morphine and codeine, whereas an opioid is any drug or endogenous agent that acts as an agonist or antagonist on one of the three major (classical) opioid receptors. Opium that contains the principal opiate, morphine,...

Eye Movement Tasks

Department of Psychology, University of Sussex, Falmer, Brighton, UK Oculomotor tasks Eye tracking Saccaddes Smooth pursuit Eye movement tasks are a powerful tool with which researchers can study the effects of pharmacological compounds on brain function. Although there are several different classes of eye movements (see Leigh and Zee 2006), two types are particularly relevant to psychopharmacological research. Saccadic eye movements are rapid, conjugate movements of the eyes, which serve to...

Memantine A7 Nachr Donepezil

Donepezil was the second cholinesterase inhibitor which became available for the symptomatic treatment of DAT. It is a noncompetitive, reversible AChE inhibitor ( Acetylcholinesterase inhibitors as cognitive enhancers) with a high central versus peripheral cholinomimetic specificity and a long duration of inhibitory action. In large-scale clinical studies it was shown to be a well-tolerated drug that causes improvement of cognitive and global function in mild to...

Beyond Inhibition of MAO

The MAOIs are multifaceted drugs and have been reported to bind to a wide variety of other enzymes, receptor systems, and uptake pumps that may contribute to their therapeutic and or adverse effects. Depending on the MAOI involved, interactions with the following have been reported other amine oxidases various transami-nases, decarboxylases, dehydrogenases, cytochromes P450 (CYPs) biogenic amine receptors and transporters imidazoline binding sites and sigma receptors (Holt et al. 2004). Several...

Black Box Warning Definition

A black box warning, also called a boxed warning or black label warning, is an FDA requirement for drugs that require close monitoring or are associated with potentially dangerous side effects that must be clearly disclosed in product labeling. Danielyan A, Kowatch RA (2005) Management options for bipolar disorder in children and adolescents. Paediatric Drugs 7(5) 277-294 DelBello MP, Findling RL, Kushner S, Wang D, Olson WH, Capece JA, Fazzio L, Rosenthal NR (2005) A pilot controlled trial of...

Acamprosate

Heyser2 1Committee on the Neurobiology of Addictive Disorders, Pearson Center for Alcoholism and Addiction Research, The Scripps Research Institute, TPC-5, La Jolla, CA, USA 2Department of Psychology, Franklin and Marshall College, Lancaster, PA, USA Calcium acetylhomotaurinate Campral Definition Acamprosate, marketed under the brand name Campral, is an orally administered drug approved in the USA and throughout much of the world for treating alcohol abuse and...

Disulfiram

Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, Charlottesville, VA, USA Tetraethylthiuram disulphide Definition Disulfiram is one of several aldehyde dehydrogenase (ALDH) inhibitors that increase the plasma level of acetaldehyde in the body following the ingestion of ethanol. Disulfiram is currently used in the treatment of alcoholism. As early as 1937, it was realized that exposure to disulfi-ram (tetraethylthiuram disulphide) resulted in abstinence from...

Construction of a Dialysis Probe

Dialysis Probe

At present, the type of dialysis probe most commonly used has a concentric structure (Fig. 1). This kind of probe has been used in a wealth of experimental research Microdialysis. Fig. 1. Schematic representation of a concentric microdialysis probe made up of the following components (see text for details) 27 gauge stainless steel tubing (1), 25 gauge stainless steel tubing (2), epoxy resin (3 and 9), dental cement (4), hot-melt adhesive (5), polyethylene tubings (6 and 11), fused silica...

Behavioral Effects of Nicotine in Humans and Animals

Nicotine exerts a plethora of acute behavioral effects, which is unsurprising given that nAChRs are very widely expressed in the brain and elsewhere. Certain behavioral effects depend not only on the dose administered, but also on recent or remote drug history some effects undergo transient or persistent tolerance, whereas others show sensitiza-tion or else remain largely stable across repeated tests. Comparison of behavioral effects in humans versus animals is hindered by several factors....

M2 Muscarinic Receptor Preferring Drugs

Another pharmacological approach to modify brain cho-linergic activity has been through M2 muscarinic acetyl-choline receptors. Some M2 muscarinic acetylcholine receptors are found to be heteroreceptors in different brain regions. However, many M2 receptors act as autoreceptors providing negative feedback at cholinergic terminals. The localization of M2 muscarinic acetylcholine receptors on cholinergic neuron terminals has led to the examination of M2-preferring antagonists on brain...

Dronabinol

Dronabinol is a synthetic form of D9-tetrahydrocannabi-nol, the main psychoactive substance in marijuana cannabis. It is a cannabinoid agonist acting on cannabi-noid CB1 and CB2 receptors. The cannabinoid CB1 are mostly located in the brain and involved in addictive properties of marijuana the CB2 receptors are located in the periphery notably in the immune system, but may be also located in the brain. Dronabinol has been used in AIDS-related anorexia associated with weight loss and in nausea...

Etizolam Definition

Etizolam is a benzodiazepine that has anxiolytic, anticon-vulsant, hypnotic, sedative, amnesic, and muscle-relaxant properties. It is used for short-term treatment of insomnia, anxiety, and panic attacks. Alpha-hydroxye-tizolam is an active metabolite that is eliminated more slowly with an half-life of 8 h. Etizolam differs from other benzodiazepines in that the molecules possess a thiophene ring instead of a benzene ring. Cases of increased prolac-tin and neuroleptic malignant syndrome, which...

Gs

AOnly selected compounds are shown for purposes of comparing mechanisms drug classes using data from two major classes of punishment procedures. Only data from systemic dosing are included. Only data from acute dosing are included. Anxiolytic-like effects of some compounds in these assays have been reported in the literature but with other procedures suggested to detect anxioltyic mechanisms (e.g., endocannabinoid uptake or enzyme inhibition mGlu8 agonists gabapentin). It must also be noted...

Distress Vocalization

NIMH Non-Human Primate Research Core, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, uSA Alarm calls Crying Isolation calls Separation calls ultrasonic vocalizations Mammalian vocalizations are the product of respiratory and laryngeal activities under the direct control of brain stem cranial and spinal motor neurons and modulated by higher brain processes (Miczek et al. 1995 Newman 2007). Distress vocalizations are sounds produced in the presence of painful,...

Fluvoxamine

Fluvoxamine is a selective serotonin reuptake inhibitor (SSRI). It was one of the earliest of these drugs to be developed and widely marketed. Although originally released as an antidepressant, it is now commonly used in the treatment of obsessive-compulsive disorder. Fluvoxamine is also used to treat other anxiety disorders (e.g., panic disorder, social anxiety disorder). As with other SSRIs, the most common troublesome side effect of fluvoxamine is sexual dysfunction (dysorgasmia and erectile...

Preclinical and Clinical Evidence of GSK3 Inhibition in the Pathophysiology and Treatment of Bipolar Disorder

As in the case of PKC inhibition, GSK activity is also inhibited by lithium and valproate, agents with mood-stabilizing properties in humans. Lithium inhibits GSK-3 through a combination of direct binding to this kinase and increased phosphorylation of its inhibitory N-terminal serine (Martinez et al. 2006). Direct inhibition of GSK-3 at therapeutically relevant concentrations of lithium occurs in vitro and in vivo, and in diverse cell types, including cultured neurons and rodent brain,...

Principles and Role in Psychopharmacology Basic Concepts

The concept of modeling psychopathology in animals is as old as the use of animals in psychological investigations its roots may be found in the work of Pavlov, Watson, and even earlier. However, for many years, practical attempts to devise animal models were sporadic, ad hoc, and unconvincing. As a result, animal models of psychiatric states were until recently viewed with justified suspicion. Over the last 20-30 years, this situation has changed, with the recognition that animal models can...

Vaccines and Drug Specific Antibodies

Pentel2 division of Clinical Pharmacology, Department of Medicine, Minneapolis Medical Research Foundation and University of Minnesota, Minneapolis, MN, USA 2Departments of Medicine and Pharmacology, Minneapolis Medical Research Foundation and University of Minnesota, Minneapolis, MN, USA In the context of psychopharmacology, vaccines are drug-protein conjugates that stimulate a subject's immune system to produce drug-specific antibodies that can bind a drug of interest...

Operant Chamber Definition

Experimental apparatus to record the behavior of animals. The quintessential operant chamber is the Skinner Box'' designed by B.F. Skinner (1904-1990) to study This term is now mostly historical (opioid is now more commonly used) but strictly refers to drugs derived directly from opium. This includes morphine (the major alkaloid in opium), codeine, and thebaine. Drugs derived by chemical modification of morphine and codeine are also sometimes referred to as opiates. These include heroin,...

Anxiolysis via a2 Gabaa Receptors

The differentiation of GABAA receptors by knock-in point mutations showed that it was the a2- but not the a3- or a5-GABAA receptor that mediated the anxiolytic activity of diazepam. In a2(H101R) mice, but not a3(H126R) or a5(H105R) mice, diazepam failed to induce anxiolytic activity (light dark paradigm, elevated plus maze). In keeping with this notion, the benzodiazepine site ligand L-838417, which showed efficacy at a2, a3, and a5, but not at a1GABAA receptors, was proved to be anxiolytic in...

GABAergic Transmission Definition

GABAergic transmission refers to activation of GABA receptors and release of GABA by endogenous or pharmacological modulators. g-Aminobutyric acid (GABA) is the most prevalent inhibitory neurotransmitter in the mammalian central nervous system. Alcohol or Alcohol Abuse and Dependence Premenstrual Dysphoric Mood Disorder Gabapentin acts on GABA receptors to produce anticonvulsant effects and is also used in the management of neuropathic pain. Its half-life is 5-7 h it is not metabolized in the...

Inverse Agonists or Neutral Antagonists Clinically Which Is Better

The majority of current therapeutic agents on the market are clinically utilized as antagonists. With respect to GPCRs, it has been estimated that approximately 85 of ligands classified as antagonists are actually inverse agonists (Kenakin 2004), assuming the endogenous receptor is constitutively active (which may well depend on tissue expression and or disease). This finding has both theoretical and practical implications. On theoretical grounds, it is to be expected that most ligands will...

Overarousal Sertraline

This methodology provides a large enough sample to detect differences between active agents. Escitalopram has demonstrated modest but consistent advantages over other SSRIs, but these differences were most significant in the comparisons with citalopram. Using a ''multiple-treatments meta-analysis'' method, which includes both direct and indirect comparisons of drugs, the efficacy and acceptability of 12 new-generation antidepressants (including the 6 SSRIs) were compared across...

Neuroprotection and Neurotoxic Amphetamines

3,4-Methylenedioxymethamphetamine ( MDMA or ecstasy) is an amphetamine and a commonly used recreational drug, often ingested at warm and crowded dance clubs and raves. There is substantial evidence that the compound produces long-lasting neurotoxic changes in the brains of experimental animals. In the rat, MDMA, given either as a single high dose or several lower doses over a relatively short period of time, induces a long-term loss of 5-hydroxytryptamine (5-HTor serotonin) nerve terminals in...

Opioid Dependence and Its Treatment

Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria Opioid dependence is a medical condition characterized by an individual's preoccupation with and strong desire to take opioids coupled with persistent drug-seeking behavior. It involves a sense of compulsion to consume the psychoactive substance, an inability to stop using it or to control the mode of drug-taking behavior. Obtaining the drug takes on high priority and the condition is frequently...

The Origins of the Term Psychopharmacology

There is little doubt that psychopharmacology came of age in the 1950s with the ascent of behavioral pharmacology and the appearance of the first antidepressants and antipsychotic drugs. The first textbook of psychopharmacology (Wolfgang de Boor's Pharmakopsycologie und Psychopathologie) was published in 1956. Experimentation with psychotropic drugs, however, had been going on for many years before. The term psychopharmacolo-gy'' was used for the first time by David I. Macht in a paper titled...

Mpr

Commonly used AMPAR antagonists are the quinoxaline-diones (such as DNQX and CNQX), which are potent non-NMDA antagonists with selectivity for AMPAR (20-fold) over KARs. Tezampanel is a competitive AMPA GluK1 antagonist with increased potency, and its orally active prodrug NGX426 is the first AMPA KAR antagonist to be studied in clinical trials for chronic pain, including migraine and neurophatic pain. Some derivatives of tezampa-nel are functioning as selective KAR GluK1 antagonists (LY382884...

Tmj

Lader argued that this use of BZs medicalized social problems It is much cheaper to tranquilize distraught housewives living in isolation in tower blocks with nowhere for their children to play than to demolish these blocks, and to rebuild on a human scale, or even to provide playgroups. An educational campaign to make doctors realize the more nebulous dangers of our present scale of use of the benzodiazepines is urgently needed. Malcolm Lader then appeared on the BBC an activist...

Adhd

No effect on cannabis use, concerning side effects (GI) Norepinephrine and dopamine reuptake inhibitor Reduced effects of smoked cannabis, but exacerbated cannabis withdrawal symptoms Serotonin 5HT1A receptor partial agonist Reduced cannabis use, craving, and irritability in pilot study effects not replicated in placebo-controlled clinical trial Reduced tachycardia, but not subjective effects Bipolar disorder, epilepsy, migraines No effect on cannabis use increased withdrawal and effects of...

Reserpine Definition

Reserpine is an indole alkaloid with antipsychotic and antihypertensive properties. It is currently not in clinical use for psychiatric conditions. Reserpine was isolated in 1952 from the dried root of Rauwolfia serpentina (Indian snakeroot), which was used in India for centuries to treat insanity and high blood pressure. Reserpine blocks the vesicular monoamine transporter, thereby acutely inhibiting the reuptake of the monoamines into the synaptic vesicles and increasing monoamine...

Principles and Role in Psychopharmacology

It was found early that antipsychotic drugs for the treatment of schizophrenia had the ability to produce a selective suppression of active avoidance conditioned avoidance behavior in rats (Cook and Weidley 1957). Later, as more antipsychotic drugs came on the market, it was found that this was a unique property among antipsychotics that was not shared by other classes of pharmacological agents, and that the selective suppression of conditioned avoidance response (CAR) produced by the...

Negative Reinforcement Theory Definition

Like positive reinforcement, negative reinforcement increases the likelihood that a behavior associated with it will be continued. However, a negative reinforcer is an unpleasant stimulus that is removed after a behavioral response. Negative reinforcers can range from uncomfortable physical sensations to actions causing severe physical distress. Taking drug to relieve the withdrawal distress is, arguably, an example of negative reinforcement. If a person's withdrawal syndrome (stimulus) goes...

History

Appetite suppressants have traditionally been used to distract patients from feelings of severe hunger and for weight control. However, appetite suppressants provide only an option for weight management and historically numerous devices, diets, and other pharmacological treatments have been employed to control body weight. The commercialization of weight control products dates from the start of the mass production of these products and a plethora of dieting products have since been marketed....

Pgs

These drugs have limited efficacy and cannot be used ubiquitously across all disorders where cognitive enhancement might be beneficial (for example, they are inappropriate for the use in patients with Parkinson's disease as they can aggravate the motor disability). Therefore, the future development of a range of drugs with different mechanisms of action is likely to occur. Ionotrophic glutamate receptors as a target for cognition enhancement have been of interest since the...

Ycl

Contingency Management in Drug Dependence. Fig. 1. Percent of patients retained for the recommended 24 weeks of treatment (top panel) and percent of patients achieving two or months of continuous cocaine abstinence during treatment (bottom panel). * indicates a significant difference between conditions (p < 0.05). (Adapted from Higgins et al. 1993.) CM has been used with subpopulation, special subpopulation such as pregnant cigarette smokers (Heil et al. 2008). Eighty-two women who were still...

Blood Brain Barrier

Department of Pharmaceutical Sciences, Inserm U705, UMR CNRS 7157, University Paris Descartes, Neuropsychopharmacology Research Unit, Paris, France Hematoencephalic barrier Neurovascular unit Definition Regions of the brain where capillary endothelial cells express unique anatomical properties such as high-resistance tight junctions and selective biochemical properties of metabolism and transport, allowing the regulation of solute exchange between blood and brain. Current Concepts and State of...

Usa

A. Franken Erasmus University Rotterdam, Institute of Psychology T13-12 P.O. Box 1738 Rotterdam 3000 The Netherlands franken fsw.eur.nl NeuroHealth Alpert Medical School of Brown University 227 Centerville Rd Warwick, RI 02886 USA joseph_friedman brown.edu Kim Fromme Department of Psychology The University of Texas at Austin 1 University Station, A8000 Austin, TX 78712 USA CNS Discovery Functional Neuroscience John Geddes University of Oxford Warneford...

Modulation of Chronic Pain Spinal a2 and a3 GABAa Receptors

The canonical circuits of GABAergic control of principal cells also applies to circuits in the spinal cord with particular reference to sensory pain processing. Using the point-mutated mice described earlier, spinal a2 (and a3) GABAA receptors were identified as powerful gatekeepers of pain (Knabl et al. 2008). The experimental a2 a3 receptor ligand L-838 417 (Table 2) was highly effective in suppressing inflammatory and neuropathic pain, yet devoid of unwanted sedation and motor impairment....

Oxm

Understood, most conditioned physiological responses to drugs can be seen to conform to the conditioning paradigm developed by Pavlov. A useful paradigm for the behavioral evaluation of conditioned drug effects is conditioned activity. Pickens and Crowder (1967) were among the first to report that environmental stimuli paired with the psychomotor-stimulant drug amphetamine produced conditioned locomotor activity in rats. In this paradigm, the CR is not a specific operant but rather a general...

F

F is measured by comparing the AUC for oral and i.v. doses from zero to the time point for which elimination is complete. The calculation of F requires an intravenous reference, that is, a route of administration that guarantees the entire administered drug reaches the systemic circulation. Such studies come at considerable cost, not least because of the necessity to conduct preclinical toxicity tests to ensure adequate safety. Bioavailability is usually calculated by determining the maximum...

L655 708

Partial inverse agonist with preference for a5 subtype B. Modulatory site other than benzodiazepine site High sensitivity (> 3 mM) at a4(a5)b35d Medium sensitivity (> 30 mM) at a4(a5)p2Sd Low sensitivity (> 100 mM) at a4(a5)b3g2 High sensitivity at 5-containing subtypesd and at a1, a3 receptors in combination with b1 Intravenous anesthetics (Etomidate, Propofol) Act on receptor subtypes containing b3, i.e., mainly a2 and a3 subtypes Partial agonist at a,, a3 subtypes, full agonist at a5,...

Role of Pharmacotherapy Kleptomania

Kleptomania is characterized by repetitive, uncontrollable stealing of items not needed for one's personal use, and is associated with significant morbidity and morality. The onset of this disorder occurs typically in early adulthood but has been reported in cases as young as four and as old as 77. The course of the illness is generally chronic, with waxing and waning of symptoms. Women appear twice as likely to suffer from kleptomania as men. Individuals with kleptomania frequently hoard,...

Open Field Test

Round Rat Open Field Test Analysis

INSERM U930, Universite Francois Rabelais Sciences et Techniques, Tours, France Open-Field Test. Fig. 1. A mouse in a circular open field - Dimensions of the arena 40 cm diameter and animals have also been allowed free access to the arena from their familiar nest. In this free confrontation situation, rodents will generally show avoidance for the brightly lit environment before entering the arena, the animal will show risk assessment postures directed toward the open field. This is a first...

Sht6

Table 2. Antidepressants in development novel serotonin-linked mechanisms. Antidepressants Recent Developments. Table 2. Antidepressants in development novel serotonin-linked mechanisms. Approved EMEA with liver monitoring, Phase III depression in the USA

Tsst

The Trier Social Stress Test (Kirschbaum et al. 1993) is a protocol for the induction of moderate to intense psychosocial stress under laboratory conditions. It comprises a 3 min anticipatory period, a 5 min public speaking task, and a 5 min mental arithmetic task in front of an evaluative panel of two adults. The TSST can be employed in adolescents and adults of all ages a slightly modified version is used when studying children from the age of 7 years and older (TSST-C). Today, the TSSTis the...

Rvc

ANaturally occurring camphor was obtained from Cinnamomum camphora since ancient times bIn 1871, there was the first recorded use of lithium for the treatment of mania and in 1886 lithium carbonate was used for the first time to prevent depression psychiatry began in the 1850s, with the invention of the hypodermic needle. Potassium bromide, first isolated from seawater in 1826, was initially used to treat scrofula and only later as an anticonvulsant. Its sedative effects began to be widely...

Hmu

Became apparent that it was less effective and more toxic than chlorpromazine and other neuroleptics. In the 1960s and 1970s, the search for new antipsychotic drugs followed two main paths. The first one (the me-too approach) consisted in altering the structure of phenothia-zine e.g., by adding a trifluoromethyl group to prometha-zine to obtain trifluoperazine. A slightly different approach consisted in using, instead of the phenothiazine rings, other tricyclic (e.g., thioxanthine) or...

Flb

The Development of New Medicines for the Health Care Market The development of new medicines has generated ethical problems that have been dealt with legal norms and strict regulations. In spite of the fact that modern pharmacology has contributed to a better quality of life for many patients all over the world, the issue of the advantages of new (and expensive) drugs versus older (and cheaper) ones is today a hot one. This is a typical case of conflict of values between doctors on one side and...

References

American College of Neuropsychopharmacology (1968) Psychopharmacology a review of progress, 1957-1967 In Efron DH (ed). US Government Printing office, Washington Ban TA (2001) Pharmacotherapy of mental illness a historical analysis. Prog Neuropsychopharmacol Biol Psychiatry 25 709-727 Carlsson A (1990) Early psychopharmacology and the rise of modern brain research. J Psychopharmacol 4 120-126 Domino EF (1999) History of modern psychopharmacology a personal view with an emphasis on...

Other Models of Parkinsons Disease PD

1-Methyl-4-Phenyl-Tetrahydropiridine (MPTP) MPTP was discovered as a by-product of a failed illegal synthesis of meperidine analogs, when it caused a profound parkinsonian syndrome in drug addicts who self-administered the substance. The peripheral administration of the drug in monkeys and mice induces major mesencephalic DA cell loss and a similarly marked PD-like motor syndrome. As in the idiopathic disease, MPTP-induced PD is responsive to L-DOPA. MPTP is not itself the toxic agent. Rather...

Drug Discrimination

Section of Behavioural Pharmacology, Institute of Psychiatry P048, King's College London, London, UK Cueing properties of drugs Drugs as cues Drug discrimination refers to behavioral paradigms in which the subjects learn to recognize the effects of a drug and report its presence by behavioral responses emitted to obtain reward or to avoid aversive stimuli. More formally, the presence of a drug generates an interoceptive discriminative stimulus (cue) signaling that an appropriate behavioral...

Nuu

Several derivatives of histamine have now been identified, which are more potent as agonists than histamine and are relatively selective for the H1-receptor. These include 2-(3-bromophenyl)-histamine, histaprodifen, and N-methylhistaprodifen. The role of these compounds is, however, restricted to a use as pharmacological tools. Compounds originally developed as drugs for completely different classes of receptors have also been identified as H1-receptor agonists. For example, the dopamine...

First Generation Antipsychotics

Prague Psychiatric Centre, The Department of Psychiatry and Medical Psychology, Charles University, Praha 8 -Bohnice, Prague, Czech Republic Classical antipsychotics Classical neuroleptics Conventional antipsychotics Conventional neuroleptics Major tranquilizers Old antipsychotics Old neuroleptics Traditional antipsychotics Traditional neuroleptics Typical antipsychotics Typical neuroleptics Antipsychotics introduced to the market in USA before First-generation antipsychotics (FGA) is a...

Regulation of Learning and Memory via a5 GABAa Receptors

Spatial and temporal memory is linked to oscillatory neuronal activity in the hippocampus, where the NMDA-type glutamate receptors on principal neurons have attracted most attention in modulating memory performance. However, there is a balancing control by GABAergic tonic inhibition. a5GABAA receptors are located at the base of the dendritic spines, which receive the excitatory input. When a5 receptors were partially reduced genetically, associative learning in the form of trace fear...

Dsl

Well as clock-controlled output genes. It is interesting to note that clock genes have been also found in single cells of human skin and mucosa (Bjarnason et al. 2001), furthermore, it has been shown that about 8-10 of all genes are regulated in a circadian fashion. In general, the human endogenous clock does not run at a frequency of exactly 24 h, but tends to be somewhat slower. The rhythm in human body temperature, which is timed by the biological clock has a period of about 25-h under...

Trace Amines

Baker Neurochemical Research Unit and Bebensee Schizophrenia Research Unit, Department of Psychiatry, University of Alberta, Edmonton, Alberta, Canada Arylalkylamines Microamines Definition Trace amines, which include b-phenylethylamine (PEA), tryptamine (T), phenylethanolamine (PEOH), the tyra-mines (TAs), octopamines (OAs), and synephrine (SYN) some authors include N,N-dimethyltryptamine (DMT) in this list , are amines related structurally to, but present in the brain...

Congestive Heart Failure Definition

Heart failure is a global term for the physiological state in which cardiac output is insufficient for the needs of the body. In case the low cardiac output itself is the underlying cause, this is often termed congestive heart failure. Common causes of heart failure include myocardial infarction, hypertension, valvular heart disease, and cardio-myopathy. The PDE3 inhibitor milrinone is used for the treatment of congenital heart failure. However, one of its side effects is ventricular...

Abuse Liability Evaluation

Walsh2 institute for Drug and Alcohol Studies, Virginia Commonwealth University, Richmond, VA, USA 2Center on Drug and Alcohol Research, Department of Behavioral Sciences, College of Medicine, University of Kentucky, Lexington, KY, USA The abuse liability of a drug or a class of drugs is their propensity to be abused and produce adverse public health consequences. Although much of what constitutes abuse liability of a drug arises from the pharmacological properties...

Assessing Impulsivity and Attention Deficits in Rodents

The diagnosis of ADHD is based on behavioral criteria. Many behavioral tests commonly used in human neuro-psychology have been modeled in animals. Though relatively simple tasks have been extensively used to measure locomotor activity (e.g., open field test), anxiety (e.g., elevated plus-maze), and learning and memory (e.g., radial-arm maze) in animal models of ADHD, more sophisticated tasks have been developed to specifically measure impulsivity and sustained attention. Tasks assessing...

Neuroimaging Synonyms

Brain imaging Brain mapping Definition Neuroimaging is a family of techniques used for obtaining images of the structure or the function of the human brain. Neuroimaging studies investigate structural and functional brain maturation in health or in diseases of the brain, such as schizophrenia, bipolar disorder, depression, ADHD, drug dependence, and autism. These studies often aim to find genetic and environmental markers of variance in brain structure and function over time. Through additions...

Involvement of AVPVasopressin Receptors in Psychiatric Disorders

Arginine Vasopressin Mice

Anxiety Anxiety disorders ( Generalized Anxiety Disorder) are associated with feelings of apprehension, tension or uneasiness. The amygdala is the region of the brain which is proposed to play a pivotal role in anxiety and fear. This brain structure contains high levels of vasopres-sin receptors and AVP causes excitation of amygdala neurons. Furthermore, animal studies have demonstrated a clear correlation between AVP levels and anxiety behavior ( Anxiety animal models), and data are emerging...

Generalized Anxiety Disorder

1Clinical Neuroscience Division, School of Medicine, University of Southampton, Southampton, Hampshire, UK 2University Department of Mental Health, RSH Hospital, Southampton, UK Anxiety neurosis Free-floating anxiety GAD Definition Generalized anxiety disorder (GAD) is characterized by an excessive and inappropriate worrying that is persistent and not restricted to particular circumstances. Patients have physical anxiety symptoms (such as tachycardia and tremor) and key psychological symptoms,...