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...

Info

Chronopharmacodynamic studies in man. Circadian Rhythms. Table 3. Chronopharmacodynamic studies in man. Cardiovascular active drugs Beta-blockers Antiasthmatic drugs Theophylline Aminophylline Orciprenaline Terbutaline Bambuterol Metacholine Methylprednisolone Dexamethasone Fluticasone Budesonide Ciclesonide Adrenaline Isoprenaline Terbutaline + Budesonide Acebutolol Metoprolol Atenolol Nadolol Bevantolol Oxprenolol Bopindolol Pindolol Labetolol Propranolol...

S

As the theta rhythm, which is hypothesized to allow rapid transitions between encoding and retrieval. The NMDA receptor is a major target for glutamate in the brain and its role in long-term potentiation is thought to be related to mnemonic encoding. It is no surprise that NMDA blockade using compounds such as AP5, ketamine, or MK-801, either intrahippocampal or intracerebral in rats impairs spatial learning using the Morris water maze, without affecting perceptual or motivational processes....

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...

Impact of Psychoactive Drugs

Rats and other vertebrates will work avidly to trigger delivery of electrical stimulation to certain brain sites. The potent rewarding effect produced by the stimulation (brain stimulation reward, BSR) can compete with, summate with, and substitute for the rewarding effects of natural goal objects, such as food and water. Thus, the stimulation appears to inject a signal into the central nervous system (CNS) that mimics those produced by natural rewards. Given that the electrically induced...

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...

Definition

Autism is a neurodevelopmental disorder characterized by impairments in social interaction, verbal and nonverbal communication, and restricted, repetitive, and stereotyped patterns of behavior, interests, and activities appearing before the age of three (American Psychiatric Association 1994). Its clinical manifestations and severity of impairments vary from mild to severe. The core symptoms are frequently accompanied by a spectrum of neurobehavioral derangements, including hyperactivity,...

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....

Role of Pharmacotherapy

Phenomenology of Delusional Disorders Delusional disorder is a rare condition, the lifetime morbidity risk is estimated to be less than 0.2 , the annual incidence is 1-3 new cases per 100,000 persons. The types of delusional disorder are defined based on the predominant delusional theme (Sadock and Sadock 2003). They are Erotomanic Type having a delusion of a secret lover the lover is often a famous person, a celebrity. The person with this type of delusional disorder may or may not contact the...

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

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...

Mechanisms of Action

Nicotine exerts almost all of its known actions via nicotinic acetylcholine receptors (nAChRs). Each nicotinic receptor comprises five protein subunits, arranged around a water-filled channel. The receptor is normally closed, but opens upon the binding of the agonist. Channel opening allows the passage of ions, notably Na+ and or Ca++. These positively charged species rapidly enter the cell, causing depolarization. This depolarization in turn stimulates the opening of voltage-gated ion...

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

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,...

Clinical Uses

The efficacy of using barbiturates for treating any psychiatric condition is not evaluable by modern criteria of evidence-based medicine. Randomized controlled trials versus placebo or active comparators in anxiety or sleep disorders are generally lacking. In a few comparative studies, the benzodiazepines consistently showed a more favorable risk-to-benefit ratio. Yet, regulatory bodies keep barbiturates on the pharmacopeia, e.g., in the USA. Among 13 hypnotics on the US market in 2008, three...

Pharmacological Properties

The monoamines targeted by amine depletion are typically the catecholamine neurotransmitters, dopamine and noradrenaline, and the indoleamine neurotransmitter, serotonin. Amine depletion in humans can be carried out in three principal ways 1. Through pharmacological inhibition of vesicular storage of amines in the nerve terminal 2. Through pharmacological inhibition of neurotrans-mitter synthesis 3. Through dietary-induced brain depletion of amino acids required for neurotransmitter synthesis...

Conclusin Of Psychopharmacology Drugs

In summary, selective NRIs can be divided into two main categories those that have primary activity only on nor-epinephrine receptors such as reboxetine, atomoxetine, and viloxazine, and those that have significant activity at other receptor sites in addition to norepinephrine, including secondary amine TCAs, maprotiline, and bupropion. With respect to the first group, the effects of norepi-nephrine activity alone result in increased alertness and concentration. For this reason, atomoxetine is...

Conclusion

Overeating and increased body weight are common side effects of many different psychiatric drugs and other medications. However, these phenomena are generally unwanted consequences of treatments considerable effort is directed toward ameliorating such effects, rather than exploiting them in clinical situations where facilitating appetite and increasing body mass are the desired outcomes. The majority of drugs discussed here provide uncertain benefits in terms of clinically significant appetite...

Vxn

Key kinetic properties of commonly used benzodiazepines. dopamine release, BZs have not been shown to enhance extracellular dopamine in the nucleus accumbens, but actually reduce dopamine levels (Licata and Rowlett 2008). Thus, the BZs are not capable of inducing dependence by the same mechanism as addictive drugs. The connecting mechanism between GABA-A receptors and the reduction in dopamine appears to be by a modulation in the glutamatergic transmission of ventral...

Advantages and Limitations of Microdialysis

Since its first applications, microdialysis has become increasingly popular to study brain function. The use of alternative in vivo procedures such as push-pull perfusion or voltammetry has remained constant or even declined during last years. A comparison between microdialysis and voltammetry reveals that microdialysis is applicable to most types of small molecules whereas the use of voltammetry is limited to easily oxidizable compounds such as catecholamines and serotonin. Moreover,...

Narcolepsy Definition

A chronic disorder of sleep characterized by excessive daytime sleepiness and sudden onset of sleep, without the normal transition through lower levels of arousal, and with an altered circadian pattern. Individuals with narcolepsy often experience cataplexy, which refers to sudden attacks of muscular weakness, often brought on by strong emotional states. Ian P. Stolerman (ed.), Encyclopedia of Psychopharmacology DOI 10.1007 978-3-540-68706-1, Springer-Verlag Berlin Heidelberg 2010

Behavioral Flexibility Attentional Shifting Rule Switching and Response Reversal

School of Psychology, University of St Andrews, Adaptability Cognitive flexibility Responsiveness Definition Behavioral flexibility refers to the adaptive change in the behavior of an animal, in response to changes in the external or internal environment. Ongoing behavior (which might include inactivity) is stopped or modified and new behavior is initiated. Adaptive changes in behavior can vary by degree, ranging from changes that are little more than reflexes or tropic reactions (i.e.,...

Extracellular Recording

Dickenson Neuroscience, Physiology and Pharmacology, University College London, London, UK Measurement of neuronal activity Definition Extracellular recordings are used to monitor neuronal activity from outside the cell. It provides a means to measure patterns of action potentials within many areas of the peripheral and central nervous systems. In addition, massed activity can also be recorded. The effects of pathology and drugs can be investigated over extended...

Cross References

Alcohol Abuse and Dependence Prenatal Exposure to Alcohol Withdrawal Syndrome References Driscoll CD, Streissguth AP, Riley EP (1990) Prenatal alcohol exposure comparability of effects in humans and animal models. Neurotoxicol Teratol 12 231-237 Lieber CS (1991) Alcohol, liver, and nutrition. J Am Coll Nutr 10 602-632 Lieber CS, DeCarli LM (1989) Liquid diet technique of ethanol administration 1989 update. Alcohol Alcohol 24 197-211 Lieber CS, Jones DP, Mendelson J, DeCarli LM (1963) Fatty...

Setiptiline Maleate Definition

Setiptiline Maleate is a tetracyclic antidepressant that has been used in the treatment of depression. It has antihistamine and hypnotic-sedative effects, but almost no anticholinergic effects. It is a weak inhibitor of norepinephrine reuptake in vitro and strongly stimulates the release of central norepinephrine by blocking pre-synaptic a2-adrenoceptors similar to mianserin. It also acts as a 5-HT2A, 5-HT2C, and 5-HT3 receptor antagonist. Unlike most conventional antidepressants, it has no...

Selective NRI Safety and Tolerability

The side-effect profiles of reboxetine, atomoxetine, and viloxazine can be attributed to the unwanted effects of norepinephrine, as activity at other receptors is limited. The concept of selectivity can thus be a bit deceiving. While an agent such as reboxetine is selective for the neurotransmitter norepinephrine, its activity is nonse-lective in terms of distribution, contributing to effects not only in the brain but in the body as well (Table 3). In the limbic system, the stimulation of...

Psychomotor Performance in Humans

University of Surrey, St Margaret's - at- Cliffe, Kent, UK Synonyms Psychomotor function Skilled performance Definition Humans have an innate capacity to react to environmental stimulation which, by way of learning and experience, develops into a range of coordinated motor behaviors that are appropriate responses to the sensory information perceived by an individual. These motor behaviors range in complexity from the instantaneous reflex reactions that follow the accidental grasping of a hot...

Stress Response Definition

The spectrum of physiological and behavioral adaptations coordinated by stress system mediators that defend homeostasis and or promote allostasis. Conditioned Place Preference Reinstatement of Drug Self-Administration Koob GF (2008) A role for brain stress systems in addiction. Neuron 59 11-34 Lu L, Shepard JD, Scott Hall F, Shaham Y (2003) Effect of environmental stressors on opiate and psychostimulant reinforcement, reinstatement and discrimination in rats a review. Neurosci Biobehav Rev 27...

Operant Conditioning

Operant conditioning is the use of environmental consequences of reinforcement and punishment to modify the occurrence and form of behavior. The strength and frequency of a response can be controlled by the schedule of reinforcement and the contingent presentation of reinforcing or punishing stimuli. Hedonic properties such as pain and pleasure are often attributed to such stimuli but do not enter into their definitions, which are based upon observed changes in behavior such as the acquisition...

Jkd

Enable them to rhythmically fire action potentials and to participate in generating network oscillations in some frequency range. These membrane properties can be measured by performing intracellular recordings or patch clamp recordings. These neurons are, by virtue of their synapses from and onto other neurons, embedded in local network loops and the balance of net interactions determines the composite frequencies. Indeed, remotely located pacing structures, as is the case for thalamocorti-cal...

Advantages and Disadvantages of Microiontophoresis

The original microiontophoretic technique was developed for answering questions concerned with synaptic transmission and the neuromuscular junction. Using this preparation, it is a simple matter to microscopically examine the muscle fiber being studied, to determine the distance of the micropipette from the tissue, and to have ready access to known synaptic inputs. These advantages are not valid for the CNS. Nevertheless, with some further precautions and considerations, the technique has been...

Reboxetine Atomoxetine and Viloxazine History

Reboxetine holds the distinction of being the first truly selective norepinephrine reuptake inhibitor and has been used in the treatment of clinical depression, anxiety disorders, and attention deficit disorders. It is licensed for use in several countries but is unavailable in the USA (Fleishaker 2000). Reboxetine has been denied approval NARI Antidepressants. Table 1. Ki values in nM and reference studies. (Adapted from http pdsp.med.unc.edu .) NARI Antidepressants. Table 1. Ki values in nM...

ED50 Definition

The ED50 is a commonly used abbreviation that denotes the Effective Dose of a drug needed to produce a particular response in 50 of a population of test samples. It is a quantitative measure of the potency of a drug the smaller the ED50 value, the more potent is the substance in the test system used. The original use of the term related to drug effects of an all-or-none (quantal) nature and it was assumed that the full range of effect frequencies from 0 to 100 actually occurred. Subsequently...

Synonyms

Arousal disorders Catathrenia Confusional arousals Exploding head syndrome Nightmares Rapid eye Parasomnias usually associated with REM sleep 2. Recurrent isolated sleep paralysis 1. Sleep-related dissociative disorders 3. Sleep-related groaning (catathrenia) clinical history from the patients and family. Formal overnight polysomnography (PSG) is limited to those patients whose behaviors are violent or extremely bothersome to other individuals or which cause significant physical damage....

Hypo and Hypercortisolistic States

Health and resilience are characterized by a reactive HPA axis that is readily turned on and off. Several disease states have been associated with changes in basal and activated HPA axis responses. Thus, hypercortisolemic states usually enhance the risk for infection because of suppression of the immune system. Examples are Cushing syndrome, melancholic depression, panic disorder, anorexia nervosa, sleep deprivation, addiction, and malnutrition. Alternatively, hypocortisolism enhances the risk...

N

The CL of a drug The amount eliminated, is proportional to the concentration of the drug in the blood. The fraction of the drug in the body eliminated per unit time is determined by the elimination constant (kel). This is represented by the slope of the line of the log plasma concentration versus time. Rate of elimination equals clearance times the concentration in the blood. It can be shown that the kel equals the log of 2 divided by the t1 2 0.693 11 2 and likewise, CL kel x VD, so, CL 0.693...

Spatial Delayed Alternation

Classical paradigm for measuring short-term (often called ''working'') memory in rodents generally employing a T-maze and basing the measure of memory on the well-known tendency of rats spontaneously to alternate their spatial choices. The memory load can be increased by lengthening the delay between the first and second trials. Analogous but not equivalent to spatial delayed response task in nonhuman primates. Source localization techniques refer to a set of mathematical techniques for...

Wmu

Amphetamine, EC rats show a greater release of dopamine in the nucleus accumbens measured by in vivo micro-dialysis compared to IC rats. This enrichment-induced change is not specific to amphetamine, but appears to occur across various drugs of abuse. Alterations in reward-relevant brain regions likely play a role in the differential sensitivity of EC and IC rats to self-administer drugs of abuse. In addition to dopamine, enrichment alters drug-induced glutamate release as measured by...

Allosteric Potentiating Ligand Definition

Allosteric antagonists or agonists produce unique effects by binding to a site on the receptor to produce a bias in the receptor conformation. Allosteric modulators of nico-tinergic receptors are compounds that interact with the receptor via binding sites that are distinct from those for acetylcholine and nicotinic agonists and antagonists. Consequently, modulators are not directly involved in the neurotransmission process they affect and hence usually do not induce compensatory processes, as...

Neuroplasticity Definition

A general term referring to changes in information content and processing within neural networks, instantiated by a large variety of biophysical changes of constituent neurons embracing molecular to cellular to higher scales of observation. Changes in neuronal gene-expression correspond to phenotypic changes, including, but not limited to, alterations in neuronal excitability, neuro-transmitter release and receptor densities, location and number of axodendritic synaptic contacts, and branching...

Foetal Alcohol Spectrum Disorders

TMR Health Professionals, Belfast, Northern Ireland Alcohol-related neurodevelopmental disorder FAS FASDs Foetal alcohol syndrome Foetal Alcohol Spectrum Disorder(s) are umbrella terms used to describe conditions arising in the infant, child and, later, adult, resulting from a confirmed range of prenatal alcohol exposure be it acute or chronic or low, high, or binge dose variety. There are two diagnostic categories 1. Foetal Alcohol Syndrome (the Facial Dysmorphol- (a) Evidence of a...

Mwk

Verbal and Non-Verbal Learning in Humans. Fig. 4. Success in novel word learning in subjects receiving placebo or L-dopa (mean values with standards errors of the means for two daily sessions with 200 trials each). In addition, also shown are results in the subgroup (n 10) receiving relatively higher doses of L-dopa because their body weights were below the group median. Scores for the reassessments and transfer sessions also are displayed. (From Knecht et al. 2004.) improved in chronic stroke...

Hxe

Implications to Other Psychiatric Symptoms and Disorders CCK is found in mesetelencephalic dopaminergic neurons that are implicated in schizophrenia. CCK inhibits dopaminergic activity, changes in the number of CCK expressing neurons have been reported in patients, and thus CCK peptides have been tested in clinical studies as adjuncts to standard antipsychotic treatment (Reeve et al. 1994). It is now known that the interaction between CCK and dopamine neurons takes place at several sites in the...

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Intracellular signaling cascades involved in the long-term stabilization of mood by lithium (Li) and valproic acid (VPA). Activation of receptors coupled to PI hydrolysis results in the breakdown of phosphoinositide 4,5-biphosphate (PIP2) into two second messengers IP3 and diacylglycerol (DAG), which is an endogenous activator of PKC. Lithium is an uncompetitive inhibitor of inositol monophosphatases, whereas both lithium and VPA, upon chronic administration, decrease...

Pharmacological Properties History

Alcohol is thought to be the earliest drug in common use, probably dating back to the paleolithic age (around 8,000 bc). Initially, alcoholic drinks were obtained through yeast-induced conversion of sugars (fermentation) from a variety of carbohydrate-based liquids, such as honey and grains steeped in water or fruit vegetable juices. Fermentation-obtained beverages have a maximum alcohol content of about 12 , since alcohol concentration above that level causes the yeast to die, thus preventing...

Tryptophan Depletion

Department of Psychiatry, McGill University, Montreal, QC, Canada Dietary tryptophan depletion Rapid tryptophan depletion Acute tryptophan depletion ATD is a technique designed to investigate directly the effects of low serotonin levels in humans. Participants in ATD studies ingest an amino acid mixture that is devoid of tryptophan. This lowers brain tryptophan and, therefore, brain serotonin synthesis. Principles and Role in Psychopharmacology Principles of ATD Ingestion of an amino acid...