The effect of various phenothiazines and tricyclic antidepressants on the accumulation and release of (3H)norepinephrine and (3H)5-hydroxytryptamine in slices of rat occipital cortex.

The effects of various structurally related tricyclic antidepressants and phenothiazines on the accumulation of (3H)-5-hydroxytryptamine, [(3H)5-HT] and (3H)norepinephrine [(3H)NE] and on the release of previously accumulated (3H)5-HT and (3H)NE were determined in slices of rat occipital cortex. Results may be summarized as follows: 1) Each compound was a better inhibitor of accumulation [both of (3H)5-HT and (3H)NE] than it was a releasing agent. 2) The hydroxylation of tricyclic antidepressants made little difference in the potencies of the compounds as inhibitors of both (3H)NE and (3H)5-HT accumulation. 3) The N-dimethylated phenothiazines and tricyclics (tertiary amines) were better inhibitors of (3H)5-HT accumulation than their corresponding secondary amines. 4) The change from a dimethylene bridge in the tricyclic antidepressants to an S atom in the phenothiazines led to a considerable decrease in the potency of the compounds as inhibitors of (3H)5-HT accumulation, but made less difference in the (3H)NE accumulation system.