MIGRAINE THERAPY - RELATIONSHIP BETWEEN SEROTONERGIC CONTRACTILE RECEPTORS IN CANINE AND RABBIT SAPHENOUS VEINS TO HUMAN CEREBRAL AND CORONARY-ARTERIES

Canine and rabbit vascular contractile responses to serotonergic agoni sts have been used to predict antimigraine efficacy for several antimi graine agents, including sumatriptan. The purpose of the present study was to establish the assumed predictive value of contractile response s in canine and rabbit saphenous veins to contractile efficacy for a s eries of agonists in human cerebral and coronary arteries and to under stand better the receptors mediating such responses. The canine and ra bbit saphenous veins contracted similarly (both qualitatively and quan titatively) to a series of structurally diverse serotonergic agonists, suggesting that the receptors mediating serotonin-induced contractili ty in these tissues were similar. In addition, the contractile potency (estimated as EC50 values) for these structurally diverse serotonergi c agonists in either the rabbit or canine saphenous vein significantly correlated with contractile potency for these agonists in human cereb ral arteries. Thus, to the extent that contractile responsiveness of h uman cerebral arteries may predict antimigraine agents, contractile re sponses of the rabbit and/or canine saphenous vein may be useful surro gates for antimigraine efficacy. In addition, the contractile potency for this series of serotonergic agonists in the rabbit or canine saphe nous vein significantly correlated with contractile potency of these a gonists in human coronary arteries. These data suggest that the use of the saphenous vein to identify potent vasoconstrictors will also reve al agents capable of contracting human coronary arteries, a liability for using this approach to evaluate promising antimigraine therapies.