By Susan A. Minchin, John G. Csernansky (auth.), Professor John G. Csernansky (eds.)
Antipsychotic medicines have been first found in 1953, and never because the overdue Seventies has the instruction manual of Experimental Pharmacology taken up this subject. a brand new therapy of this subject will be due less than any conditions; even though, this can be now quite precise, seeing that extraordinary development has been made on a number of fronts in furthering our figuring out of the mechanisms of antipsychotic drug motion. First, we've got realized that schizophrenia is an disorder with particu lar neuroanatomical abnormalities, lots of which recommend that the disease is brought on by blunders in neurodevelopment. those findings have helped to shape a context for realizing neurochemical aberrations within the affliction and recommend new methods for pharmacological remedy. Propelled ahead via quick advances in neurochemical anatomy, present pathophysiological hypotheses of schizophrenia and antipsychotic drug motion have taken at the visual appeal of complicated electric circuit diagrams. moment, molecular biology stories have now printed that there's a multiplicity of dopamine receptors (i. e. , D , DZshort' j DZlong, D , D , and D ), a few of that can develop into solely new objectives for three four s antipsychotic drug motion. mockingly, the advance of substances which are selec tive for those receptors and that may be used to enquire their functionality lags at the back of; but the invention of those new receptors bargains exceptional opportu nities for constructing medications with stronger efficacy and less aspect effects.
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In fact, the difference between affinities of the typical and atypical drugs, as measured by pK j , is statistically significant and has been suggested to account for differences between typical and atypical drugs related to side-effect profile and patterns of symptom response (MELTZER et al. 1989). II. Combined DzlD 3 Antagonists Several substituted benzamides with high affinity for the D2 receptor have also been shown to bind to D3 receptors. Sulpiride has long been used as an antipsychotic drug, and found to produce relatively mild extrapyramidal side effects (ALFREDSSON et al.
Psychiatr Clin North Am 16(3):567-587 Meco G, Bedini L, Bonifati V, Sonsini U (1989) Risperidone in the treatment of chronic schizophrenia with tardive dyskinesia. Curr Ther Res 46:876-883 Meltzer HY (1980) Relevance of dopamine autoreceptors for psychiatry: clinical and preclinical studies. Schizophr Bull 6:456-475 Meltzer HY (1989) Clinical studies on the mechanism of action of clozapine: the dopamine-serotonin hypothesis of schizophrenia. Psychopharmacology 99:S18S27 Meltzer HY (1991) The mechanism of action of novel antipsychotic drugs.
Phenothiazines These drugs were the first major class of antipsychotics to be developed, and members of this class are still widely used today. In addition, this class is the largest, due to the large number of derivatives of phenothiazine synthesized since 1950. Phenothiazine is a three-ring heterocyclic compound in which two aromatic rings are linked by a third ring containing sulfur and nitrogen atoms (see Fig. 1). There are three subclasses in this family of antipsychotic drugs, based on differences in the composition of the side chain linked to the nitrogen atom in the phenothiazine nucleus (position 10): (1) aliphatics, (2) piperidines, and (3) piperazines.