Antipsychotic drugs pharmacology

Ahlenius, S. (1999) Clozapine dopamine D, receptor agonism in the prefrontal cortex as the code to decipher a Rosetta Stone of antipsychotic drugs. Pharmacology Toxicol 84 193—196. 

The answer is c. (Hardman, pp 414-4163) Unwanted pharmacologic side effects produced by phenothiazine antipsychotic drugs (e.g., perphenazine) include Parkinson-like syndrome, akathisia, dystonias, galactorrhea, amenorrhea, and infertility. These side effects are due to the ability of these agents to block dopamine receptors. The phenothiazines also block muscarinic and a-adrenergic receptors, which are responsible for other effects. 

Suessbrich, H., Schonherr, R., Heinemann, S.H., Attali, B., Lang, F. and Busch, A.E. (1997) The inhibitory effect of the antipsychotic drug haloperidol on HERG potassium channels expressed in Xenopus oocytes. British Journal of Pharmacology, 120, 968-974. 

Titier, K., Canal, M., Deridet, E., Abouelfafh, A., Gromb, S., Molimard, M. and Moore, N. (2004) Determination of myocardium to plasma concentration ratios of five antipsychotic drugs comparison with their ability to induce arrhythmia and sudden death in clinical practice. Toxicology and Applied Pharmacology, 199, 52-60. 

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. 

TABLE 34.1 Pharmacological Distinctions Among Representative Antipsychotic Drugs... 

Fatenri, SJT., Meltzer, H.Y., Roth, B.L. Atypical antipsychotic drugs clinical and preclinical studies. In Csemansky, J.G. (ed.) Experimental Handbook of Pharmacology. Antipsvehotics . Springer Verlag, Beilin, 1996, pp. 77—115. 

It is a potent antipsychotic drug. It does not cause weight gain. Its pharmacological effects are similar to phenothiazines. 

Meltzer HY. Pre-clinical pharmacology of atypical antipsychotic drugs a selective review. Br J Psychiatry 1996 168(suppl 29) 23-31. 

Three subfamilies of phenothiazines, based primarily on the side chain of the molecule, were once the most widely used of the antipsychotic agents. Aliphatic derivatives (eg, chlorpromazine ) and piperidine derivatives (eg, thioridazine ) are the least potent. These drugs produce more sedation and weight gain. Piperazine derivatives are more potent (effective in lower doses) but not necessarily more efficacious. Perphenazine, a piperazine derivative, was the typical antipsychotic drug used in the CATIE study described in the following text. The piperazine derivatives are also more selective in their pharmacologic effects (Table 29-1). 

Most of the unwanted effects of antipsychotic drugs are extensions of their known pharmacologic actions (Tables 29-1 and 29-2), but a few effects are allergic in nature and some are idiosyncratic. 

Perhaps the best example of this principle is the new antipsychotic drug, clozaril, which works on the serotonin and norepinephrine, as well as on the dopamine systems. Clozaril is a very dirty drug, and yet patients with severe schizophrenic psychoses—unresponsive to any of the cleaner neuroleptics—have been effectively treated with it. Once you have seen a patient who has been socially withdrawn and severely delusional for years suddenly conversing normally you quickly abandon the canon of pharmacological purity. 

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