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Loxapine

* No recognised classification system exists for atypical antipsychotics.Tentative terms based on receptor binding profiles have been applied to certain drug groupings, for example'broad spectrum atypicals' for clozapine, olanzapine and quetiapine, whilst risperidone and ziprasidone have been described as 'high affinity serotonin-dopamine antagonists'. ** Amisulpride and sulpiride are structurally related. *** Sertindole is available only on a named patient basis, f Licenced indications for thioridazine were severely restricted in 2000 after evidence emerged of cardiovascular toxicity, f In some classifications thioridazine and sulpiride are considered to be 'atypical' due to their low propensity to cause extrapyramidal adverse effects.

The reality is more complex since the receptor binding profile of clozapine and the newer atypical antipsychotic agents suggests that D2-receptor blockade is not essential for antipsychotic effect. The atypical drugs act on numerous receptors and modulate several interacting transmitter systems. Clozapine is a highly effective antipsychotic. It has little affinity for the D2-receptor compared with classical drugs but binds more avidly to other dopamine subtypes (e.g. Dv D3 and D4). It blocks muscarinic acetylcholine receptors, as do certain classical agents (e.g. thioridazine), a property which may reduce the experience of extrapyramidal effects. Clozapine binds more readily as an antagonist at (^-adrenoceptors than the classical drugs and also blocks histamine and serotonin receptors (5HT2 and others).

The newer atypical psychotropics vary widely in their receptor binding profiles. Olanzapine and quetiapine bear resemblance to the profile of clozapine in that their therapeutic effects appear to derive from action on different receptors and transmitter systems. All atypicals (except amisulpride) exhibit greater antagonism of 5HT,-receptors than D2-receptors compared with the classical agents. Atypical drugs that do antagonise dopamine D2-receptors appear to have affinity for those in the

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