Premium
The effects of 5‐HT and m‐chlorophenylpiperazine (m‐CPP) on the efflux of [3H]‐5‐HT from human perfused platelets.
Author(s) -
Carver JG,
GrahameSmith DG,
Johnson ES,
Madgwick Z
Publication year - 1993
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.1993.tb04172.x
Subject(s) - ketanserin , platelet , serotonin , agonist , endocrinology , medicine , 5 ht receptor , efflux , pharmacology , receptor antagonist , chemistry , antagonist , receptor , biochemistry
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.