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 (. D1, D3 and D4). It blocks muscarinic acetylcholine receptors, as do certain classical agents (. thioridazine), a property which may reduce the experience of extrapyramidal effects. Clozapine binds more readily as an. | PSYCHOTROPIC DRUGS SECTION 4 19 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 . Dr D3 and D4 . It blocks muscarinic acetylcholine receptors as do certain classical agents . thioridazine a property which may reduce the experience of extrapyramidal effects. Clozapine binds more readily as an antagonist at a2-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 5HT7-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 Fig. Sagittal brain section illustrating dopaminergic pathways. I. Mesolimbic pathway overactive in psychotic illness according to the dopamine hypothesis of schizophrenia .VTA ventrotegmental area. 2. Nigrostriatal pathway involved in motor control underactive in Parkinson s Disease and associated with extrapyramidal motor symptoms . 3. Tuberoinfundibular pathway inhibits prolactin release from the hypothalamus . mesolimbic system producing antipsychotic effect rather than the nigrostriatal system associated with unwanted motor effects . In contrast to classical antipsychotics risperidone shares with clozapine an ability antagonise a2-adrenoceptors a .
