Pharmacological and physiological correlates of variable receptor sensitivity.

isolated synaptosomes in line with their clinical potency. Thus trans-flupenthixol had n o action on dopamine release but the cis-isomer inhibited K+-stimulated release by 50 % a t the dose used (Fig. Jb). Further work is required t o establish whether the stimulusinduced release of K + can be extinguished by higher doses of the cis-isomer. In parallel, K+-stimulated dopamine synthesis in synaptosomes from the neuroleptic-treated rats was significantly inhibited. This inhibitory action of the drugs is similar t o that previously reported by Seeman & Lee (1975), who used striatal slices, preloaded with [3Hldopamine. In these experiments, Seeman & Lee (1975) were able t o show a good correlation between inhibition and clinical effectiveness of a range of neuroleptics. Insufficient experiments on depolarization-induced release have been carried out in the present study t o attempt a similar correlation. However, the data we have accumulated on the inhibitory action of neuroleptics on dopamine taken together with our evidence for a n inhibitory action of these neuroleptics on that synthesis of dopamine that is triggered by K+ depolarization would lead us t o the conclusion that inhibition of recently synthesized dopamine leads to a parallel decrease in its release.