Antipsychotic drugs mechanism

Baptista T. Body weight gain induced by antipsychotic drugs mechanisms and management. Acta Psychiatr Scand 1999 100(1) 3—16... 

Typical (first-generation) antipsychotic drugs - mechanism of action... 

The answer is c. (Hardman, pp 574—575.) Phencyclidine is a hallucinogenic compound with no opioid activity Its mechanism of action is amphetamine-like. A withdrawal syndrome has not been described for this drug in human subjects. In overdose, the treatment of choice for the psychotic activity is the antipsychotic drug haloperidol. 

Strange, P. G. Antipsychotic drugs importance of dopamine receptors for mechanisms of therapeutic actions and side effects. Pharmacol. Rev. 53 119-133, 2001. 

Miyamoto S, Dnncan GE, Marx CE, et al. Treatments of schizophrenia a critical review of pharmacology and mechanisms of action of antipsychotic drugs. Mol Psychiatry 2005 10 79-104. 

The predominant mechanism by which currently available antipsychotic medications interfere with dopamine activity is by blockade of dopamine receptors on neurons innervated by dopamine nerve terminals. Of the five types of dopamine receptors, all antipsychotics share in common the fact that they block the dopamine type 2 receptor, also known as the D2 receptor, to a varying degree. Some of the atypical antipsychotics also block other dopamine receptors (see Table 13.5). The role of blockade of Dl, D3, D4, and other dopamine receptors in the therapentic effects of antipsychotic drugs remains unclear. Aripiprazole is an exception to this in that it is a partial agonist at the D2 receptor. 

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. 

The earliest effective treatments for schizophrenia and other psychotic illnesses arose from serendipitous clinical observations rather than from scientific knowledge of the neurobiological basis of psychosis or the mechanism of action of effective antipsychotic agents. Thus, the fist antipsychotic drugs were discovered by accident in the 1950s when a putative antihistamine (chlorpromazine) was serendipitously observed to have antipsychotic effects when tested in schizophrenic patients. Chlorpromazine indeed has antihistaminic activity, but its therapeutic actions in schizophrenia are not mediated by this property. Once chlorpromazine was observed to be an effective antipsychotic agent, it was tested experimentally to uncover its mechanism of antipsychotic action. 

---