THE EFFECTS OF 5-HT AND M-CHLOROPHENYLPIPERAZINE (M-CPP) ON THE EFFLUX OF [H-3] 5-HT FROM HUMAN PERFUSED PLATELETS

1 m-Chlorophenylpiperazine (m-CPP), a 5-HT1c-receptor agonist, induces migraine-like headaches when taken orally by migraine sufferers. The present study was undertaken to see what effects m-CPP had on 5-HT function in platelets. 2 Platelets from healthy male volunteers were loaded with [H-3]-5-HT and continuously perfused in vitro with carboxygenated Krebs solution at 37-degrees-C. After 30 min washout the effects of m-CPP, thrombin, 5-HT and ADP on the efflux of [H-3]-5-HT were recorded. 3 m-CPP (0.5-500 muM) did not evoke an increase in the efflux of [H-3]-5-HT over that occurring spontaneously whereas thrombin, unlabelled 5-HT and ADP did. The effects of 5-HT were potentiated by ADP. The results were identical whether or not the 5-HT reuptake blocker paroxetine (1 muM) was present. 4 m-CPP inhibited the increase in the efflux of [H-3]-5-HT evoked by different concentrations of unlabelled 5-HT in the presence of ADP (2.5 muM) and displaced the 5-HT log concentration response curve to the right. A similar result was obtained with the 5-HT2-receptor antagonist ketanserin. 5 We conclude that m-CPP is a 5-HT2-receptor antagonist on human platelets, which is unlikely to account for its headache-inducing property, as many drugs effective in migraine prophylaxis have this action.