The effects of 5-HT and m-chlorophenylpiperazine (m-CPP) on the efflux of [3H]-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 [3H]-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 [3H]-5-HT were recorded. 3. m-CPP (0.5-500 microM) did not evoke an increase in the efflux of [3H]-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 microM) was present. 4. m-CPP inhibited the increase in the efflux of [3H]-5-HT evoked by different concentrations of unlabelled 5-HT in the presence of ADP (2.5 microM) 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.
Carver
J G
JG
MRC Unit, Radcliffe Infirmary.
Grahame-Smith
D G
DG
Johnson
E S
ES
Madgwick
Z
Z
D000244:Adenosine Diphosphate / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D012701:Serotonin / Q000097:blood / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology
D000244:Adenosine Diphosphate; D010879:Piperazines; D012701:Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; D013917:Thrombin; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid