Pharmacology atypical antipsychotic

Campbell M, Young PI, Bateman DN, Smith JM and Thomas SHL (1999). The use of atypical antipsychotics in the management of schizophrenia. British Journal of Clinical Pharmacology, 4,1, 13-22. 

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. 

To search for novel neuroleptic agents, attention has been given to structural modifications of dibenzoepines such as clozapine (9) [ 17] as a clinically active atypical antipsychotic, and its analogous fluperlapine (10) [18, 19] with a pharmacological resemblance to clozapine. Some 2-piperazinyl-5-phenyl-... 

P. L., McCloskey, T. C., Johnson, M.P., McCarty, D. R., Poirot, M., Senyah, Y., Siegel, B. W Widmaier, C. (1996) Preclinical characterization of the potential of the putative atypical antipsychotic MDL 100,907 as a potent 5-HT2A antagonist with a favorable CNS safety profile. The Journal of Pharmacology and Experimental Therapeutics, 277, 968—981. 

Atypical antipsychotics The second generation or so-called atypical antipsychotics have chemical, pharmacological, and clinical properties that are different from those of the classical antipsychotics/ neuroleptics. The most commonly used atypicals include clozapine, olanzapine, risperidone, and quetiapine. 

Davies, M. A., Setola, V., Strachan, R. T, et al. (2006) Pharmacologic analysis of non-syn-onymous coding h5-HT2A SNPs reveals alterations in atypical antipsychotic and agonist efficacies. Pharmacogenomics. J. 6, 42-51. 

Finkel S. Pharmacology of antipsychotics in the elderly a focus on atypicals. J Am Geriatr Soc 2004 52 S258-S265. 

More recent variants of the dopamine hypothesis have been derived mostly from the profile of actions of the atypical antipsychotic clozapine and seek to relate pharmacological findings to the clinical actions of this product. At the same time the pharmacological profile of clozapine is being used as a starting point for obtaining safer and more effective antipsychotics. Comparison of the major clinical and pharmacological effects of clozapine provides the picture shown in Table 4.1. 

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. 

Receptor-Binding Studies. Among the newer atypical antipsychotics, ziprasidone (Geodon) has a distinctive pharmacological profile ( Fig. 5-2). Binding studies indicate that ziprasidone has a high affinity for D 2 receptors, approximately equal to that of risperidone. In vitro, ziprasidone ... 

Despite the advent of the atypical antipsychotic agents, efforts continue to identify other adjunctive medications that may improve response to standard treatments. In this context, we note that there is no consistent evidence that BZD monotherapy benefits schizophrenia. Another strategy, however, is the addition of BZDs to an antipsychotic regimen. This pharmacological approach is partially based on the evidence that GABA, which is facilitated by BZDs, inhibits certain dopamine tracts and that these medications may attenuate the dopamine system via a different route ( 339, 340, 341 and 342). 

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

Moore NA, Tye NC, Axton MS, et al. The behavioral pharmacology of olanzapine, a novel atypical antipsychotic agent. J Pharmacol Exp Ther 1992 262 545-551. 

What is an atypical antipsychotic From a pharmacological perspective, the atypical antipsychotics as a class may be defined in part as serotonin-dopamine antagonists (SDAs) (Fig. 11 — 16). Several other distinguishing pharmacological characteristics will be discussed in the following section. In this section, we will first discuss how the atypical antipsychotics all derive some of their atypical clinical properties from exploiting the different ways that serotonin and dopamine interact within the four key dopamine pathways in the brain. Thus, it is very important to understand serotonin-dopamine interactions in each of the four dopamine pathways. 

Although there are obviously many other factors at play here and this is an overly simplistic explanation, it is a useful starting point for beginning to appreciate the pharmacological actions of atypical antipsychotics as a class of drugs. 

Not only do the atypical antipsychotics have incremental pharmacological actions beyond SDA actions, but they also have additional favorable and unfavorable clinical properties beyond the limited clinical definition of reduced EPS and actions on positive symptoms of psychosis. These additional favorable properties include the ability to improve negative symptoms in schizophrenic patients better than do con-... 

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