Comparative effects of clozapine and alpha-adrenoceptor blocking drugs on regional noradrenaline metabolism in rat brain.
Clozapine increased brain noradrenaline (NA) metabolism, as indicated by changes in 3-methoxy-4-hydroxyphenylglycol sulfate content, in brain regions corresponding to the predominance of alpha- over beta-receptors, i.e., hypothalamus, medulla, midbrain and cortex, but not corpus striatum or cerebellum. Phenoxybenzamine had a stronger effect in the hypothalamus than did clozapine, but did not change cortical NA metabolism within a 60 min treatment time; however, cortical NA metabolism was increased 150 min after phenoxybenzamine. The delayed effect of phenoxybenzamine may be due to either a poor affinity for some central receptors or a slow rate of entry into certain brain regions. Thioridazine and the benzodioxane, dibozane, had regional effects similar to clozapine. The similarity between clozapine and dibozane in ther effects on regional brain NA metabolism may reflect a preference for presynaptic alpha-receptors. It is unlikely that the antipsychotic activity of clozapine is related to a specific adrenolytic effect, but may reflect the combined activity of this drug on several transmitter systems.
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D003024:Clozapine / Q000494:pharmacology*; D003984:Dibenzazepines / Q000494:pharmacology*; D005260:Female; D007031:Hypothalamus / Q000378:metabolism; D008734:Methoxyhydroxyphenylglycol / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D010643:Phenoxybenzamine / Q000494:pharmacology; D051381:Rats; D013997:Time Factors
D000317:Adrenergic alpha-Antagonists; D003984:Dibenzazepines; D010643:Phenoxybenzamine; D008734:Methoxyhydroxyphenylglycol; D003024:Clozapine; D009638:Norepinephrine