Risperidone antipsychotic activity

Antipsychotic activity Many at5 ical neuroleptics (e.g. amperozide and risperidone) are 5-HT2 receptor antagonists. In animals, 5-HT3 antagonists have profiles similar to chronically active neuroleptics... 

In experimental studies, many clinically effective neuroleptics have been shown to act as 5-HT2A receptor antagonists. Studies on post-mortem brain from schizophrenic patients have shown that the decrease in the number of 5-HT2A receptors in the prefrontal cortex might be related to the disease process. It therefore seems unlikely that the antipsychotic activity of neuroleptics can be explained solely in terms of their action on 5-HT receptors. Furthermore, no correlation exists between the average therapeutic doses of a neuroleptic and its affinity for 5-HT receptors. It does seem possible, however, that several atypical neuroleptics such as amperozide, risperidone and possibly ritanserin do owe at least part of the pharmacological profile to their ability to inhibit 5-HT receptors. 

Risperidone (11) was also included among a a 1-adrenergic receptor antagonists to study a quantitative structure-activity relationship (99BMC2437). A pharmacophore model for atypical antipsychotics, including 11, was established (00MI41). An increased plasma level of 11 and 9-hydroxyrisperidone (12) was observed in combination with paroxetine (01 MI 13). The effect of vanlafaxine on the pharmacokinetics of 11 was reported (99MI13). 

A role for the 5-HT7 receptor in the regulation of circadian rhythms has been implicated. As discussed above, 5-HT has been known for some time to induce phase shifts in behavioral circadian rhythms and modulate neuronal activity in the suprachiasmatic nucleus, the likely site of the mammalian circadian clock. The pharmacological characteristics of the effect of 5-HT on circadian rhythms are consistent with 5-HT7 receptor. Moreover, mRNA for the 5-HT7 receptor is found in the suprachiasmatic nucleus. There is also increasing evidence that the 5-HT7 receptor may play a role in psychiatric disorders. The regional distribution of 5-HT7 receptors in brain includes limbic areas and cortex. Atypical antipsychotics, such as clozapine and risperidone, and some antidepressants display high affinity for this receptor. In the periphery, 5-HT7 receptors havebeenshown to mediate relaxation of vascular smooth muscle. 

The heterocyclic antipsychotic agent, risperidone, is a benzisoxazole derivative with antiserotoner-gic (5-HT2) as well as antidopaminergic (D2) activity. Risperidone is also considered to be a so-called quantitatively atypical antipsychotic agent because in low doses it has few extrapyramidal effects. 

Receptor-Binding Studies. Risperidone (Risperdal) is a benzisoxazole derivative that has a relatively high 5-HT " tio and relatively fewer and milder EPS than neuroleptics at its clinically effective doses. Receptor-binding studies of risperidone and its active metabolite, 9-OH-risperidone, in comparison with other novel antipsychotics revealed that ... 

A parenteral, depot antipsychotic is one that can be administered in such a way that, after a single dose, a therapeutically efficient tissue concentration of at least 1 week s duration is achieved (251,252). Slow release of the active drug is produced by combining the base antipsychotic with a fatty acid (decanoic acid). The alcohol group of the antipsychotic is esterified by the acid, producing a lipophilic compound whose solubility in oil is increased. An oil, usually sesame, is then used as a vehicle for intramuscular injection, where the ester, which is not pharmacologically active, is hydrolyzed by tissue esterases, slowly releasing the active compound. An alternative technique is the use of microspheres (e.g., risperidone). 

Schizophrenia is usually treated with a class of medications called antipsychotics, or neuroleptics, that act to reduce the activity of the neurotransmitter dopamine, which may be overactive in the brains of schizophrenics. Commonly used antipsychotic medications include risperidone (Risperdal ),... 

Another cytochrome P450 enzyme of importance to atypical antipsychotic drugs is 2D6. Risperidone, clozapine, and olanzapine are all substrates for this enzyme (Fig. 11—46). Risperidone s metabolite is also an active atypical antipsychotic (Fig. 11 — 47), but the metabolites of clozapine and olanzapine are not. Recall that some antidepressants are inhibitors of CYP450 2D6 and thus can raise the levels of these... 

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