Risperidone actions

Many of the neuroleptics are a-adrenoceptor antagonists. Some, like chlorpromazine, block d postsynaptic receptors while clozapine (and risperidone) are as potent at 2 as D2 receptors. There is no evidence that either of these actions could influence striatal or mesolimbic function but NA is considered important for function of the prefrontal cortex and any increase in its release, achieved by blocking a2-mediated autoinhibition, might contribute to a reduction in negative symptoms and provide a further plus for clozapine (see Nutt et al. 1997). Centrally, however, most a2-receptors are found postsynaptically and their function, and the effect of blocking them, is uncertain. 

Sleep and sedative effects of the atypical antipsychotics could be related to different mechanisms antagonism of 5-HT2 receptors, antihistaminic and antimus-carinic effects, and probably an a-1 noradrenergic effect. The difference in the effect on sleep between risperidone and haloperidol may be due to their differential actions on serotoninergic receptors (Trampus and Ongini 1990 Trampus et al. 1993). 

D2 receptor, albeit with different specificity. Older examples of dopamine antagonists are chlorpromazine, haloperidol and many derivatives of these prototype compounds. Newer antipsychotic drugs such as risperidone, olanzapine and quetiapine have retained this mechanism of action, although no longer exclusively. 

Risperidone may also cause hypotension via its a-adrenergic blocking actions ( 501). In the elderly, hypotensive side effects can occur, especially if there is any of the following ... 

Thus, most of the atypical and some typical antipsychotic agents are at least as potent in inhibiting 5-HT2 receptors as they are in inhibiting D2 receptors. The newest, aripiprazole, appears to be a partial agonist of D2 receptors. Varying degrees of antagonism of 0-2 adrenoceptors are also seen with risperidone, clozapine, olanzapine, quetiapine, and aripiprazole. The clinical relevance of these actions remains to be ascertained. 

Until recently, lithium carbonate was the universally preferred treatment for bipolar disorder, especially in the manic phase. With the approval of valproate, aripiprazole, olanzapine, quetiapine, risperidone, and ziprasidone for this indication, a smaller percentage of bipolar patients now receive lithium. This trend is reinforced by the slow onset of action of lithium, which has often been supplemented with concurrent use of antipsychotic drugs or potent benzodiazepines in severely manic patients. The overall success rate for achieving remission from the manic phase of bipolar disorder can be as high as 80% but lower among patients who require hospitalization. A similar situation applies to maintenance treatment, which is about 60% effective overall but less in severely ill patients. These considerations have led to increased use of combined treatment in severe cases. After mania is controlled, the antipsychotic drug may be stopped and benzodiazepines and lithium continued as maintenance therapy. 

Montel H, Starke K, Taube HD (1975) Morphine tolerance and dependence in noradrenaline neurons of the rat cerebral cortex. Naunyn-Schmiedeberg s Arch Pharmacol 258 415-26 Potkin SG, Saha AR, Kujawa MJ, Carson WH, Ali M, Stock E, Strinfellow J, Ingenito G, Marder SR (2003) Aripiprazole, an antipsychotic with a novel mechanism of action and risperidone vs. placebo in patients with schizophrenia and psychoaffective disorder. Arch Gen Psychiat 60 681-90... 

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. 

The atypical antipsychotics are divided into two major pharamacological groups, namely the multiple receptor antagonists, such as clozapine, olanzapine and quetiapine, and the more selective 5-HT2/D2 antagonists as exemplified by risperidone, sertindole, ziprasidone and zotepine. The benzamide antipsychotic amisulpride is the most selective antagonist for the D2/D3 receptors which presumably gives it the mesocortical selectivity of action with a minimal effect on the dopamine receptors in the basal ganglia. 

Mania has rarely been associated with classic neuroleptic drugs, but has been described in patients treated with new antipsychotic drugs, especially risperidone (SEDA-22, 69). Several cases of mania, presumably associated with olanzapine, have been reported (99,137-144). The mechanism is not clear. It has been suggested that olanzapine could lead to manic symptoms in patients with schizophrenia because of its potent anti-5HT2A action. 

When initiating long-acting risperidone formulation by intramuscular injection, onset ot action can be delayed tor 2 weeks while microspheres are being absorbed... 

Risperidone is an atypical benzisoxazole neuroleptic drug. It is a dopamine D2 receptor antagonist, with antagonistic actions at 5-HT2 receptors, alpha-adrenoceptors, and histamine Hi receptors. 

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