5ht Receptor Subtypes

Serotonin projections innervate virtually all regions of the brain. Ascending serotonergic fibers arise principally from two midbrain nuclei, the dorsal raphe (DR, B7) and the median raphe (MR, B8), and project to virtually all forebrain regions, including the thalamus, hypothalamus, caudate-putamen, hippocampus, and neocortex.9-11 Several brain regions, including the frontal cortex and hypothalamus, receive innervation from both nuclei. However, the caudate-putamen receive their main input...

The Segregation of Symptoms

The type 1 type 2 model implies that the distinction between symptoms based on symptom type is inextricably related to a distinction between acute and chronic symptoms. It does not account for the existence of chronic positive symptoms or transient negative symptoms. It does not answer the question of whether or not chronic positive symptoms and chronic negative symptoms arise from distinct pathophysiological processes. To address this issue, Liddle5,6 examined the relationships between...

What Is The Receptor Basis Of Antipsychotic Drugs Which Elicit Little Or No Parkinsonism

The D2-blocking action of antipsychotic drugs commonly elicits Parkinsonism and other extrapyramidal signs. Clozapine and quetiapine, however, cause little or no extrapyramidal signs. Other antipsychotics may also cause few extrapyramidal signs if the dose is kept low. A dominant factor in determining whether a particular antipsychotic drug elicits Parkinsonism is whether it binds more tightly or more loosely than dopamine at the high-affinity state of the dopamine D2 receptor. This is...

C5HT2 Receptors

Studies of 5-HT2 receptors in the frontal cortex of patients with schizophrenia have generated conflicting results. Early studies were performed with 3H LSD, a ligand which labels both 5-HT1 and 5-HT2 families.72 Bennett et al.73 reported decreased 3H LSD binding in the frontal cortex of patients with schizophrenia as compared to controls. Because 3H 5-HT binding was not reduced in these samples, the decreased 3H LSD binding was attributed to the 5-HT2A sites, which display relatively low...

What Is The Basis For The Apparently Low D2 Occupancy By Clozapine And Quetiapine

As noted earlier, antipsychotic drugs, when given at clinically effective doses, generally occupy 60 to 80 of brain dopamine D2 receptors in patients, as measured by PET or SPET in the human striatum (Figure 3). Clozapine, however, has consistently been an apparent exception. For example, in patients taking therapeutically effective antipsychotic doses of clozapine, this drug only occupies between 0 and 50 of brain dopamine D2 receptors, as measured by a variety of radioligands using either...

Antipsychotic Drug Effects In An Animal Model Of Schizophrenia

As noted previously, the ability of antipsychotic drugs to stimulate dopaminergic transmission, particularly within the frontal cortex, has received a great deal of attention, in part, because of the notion that schizophrenic patients may have reduced cortical dopamine transmission.50,52 The concept of reduced cortical dopamine transmission and associated cognitive and behavioral effects has long been central to neurobiological hypotheses of schizophrenia49,51,61 and to animal models of the...

The Developmental Deregulation Model

While the type 1 type 2 model of schizophrenia provides a plausible explanation for the variation in degree of persistence of symptoms, the three-syndrome model provides a more satisfactory account of the heterogeneity of symptom type. In particular, the evidence supports the hypothesis that the pathophysiology of schizophrenia disrupts the function of a diverse set of cerebral sites and that the type of symptoms is largely determined by the nature of function of the affected cerebral regions....

Potency And Efficacy Of Antipsychotic Drugs

While all antipsychotics are affective against the florid symptoms of psychosis, they differ in the dosages required to achieve their palliative effects. Therefore, one of the oldest classification schemes for antipsychotic drugs is based on their potency. The potency of antipsychotic drugs has been traditionally expressed in equivalency units as compared to 100 mg of chlorpromazine, the prototypic antipsychotic drug.2 The drugs are usually divided into high, medium, and low potency groups. The...

References

Seeman, P., Dopamine receptor clinical correlate, in Psychopharmacology The Fourth Generation of Progress, Bloom, F. E. and Kupfer, D. J., Eds., Raven Press, Ltd., New York, 1995, chap. 26. 2. Seeman, P. and Niznik, H. B., Dopamine receptors and transporters in Parkinson's disease and schizophrenia, FASEB J, 4, 2737, 1990. 3. Weinberger, D. R., Implications of normal brain development for the pathogenesis of schizophrenia, Arch. Gen. Psychiatry, 44, 660, 1987. 4. Weinberger, D. R.,...

Typical And Atypical Medications

The most widely used property-based classification of antipsychotic medication divides them into typical and atypical drugs. Unfortunately, the parameters which distinguish typical from atypical drugs have not been well defined. The narrowest definition distinguishing typical from atypical drugs relates to their capacity to induce extrapyramidal side effects. All the earlier drugs, such as chlorpromazine, fluphenazine, thiothixene, and haloperidol, were found to have a strong tendency to...