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 agonists have been used to predict antimigraine efficacy for several antimigraine agents, including sumatriptan. The purpose of the present study was to establish the assumed predictive value of contractile responses in canine and rabbit saphenous veins to contractile efficacy for a series of agonists in human cerebral and coronary arteries and to understand better the receptors mediating such responses. The canine and rabbit saphenous veins contracted similarly (both qualitatively and quantitatively) to a series of structurally diverse serotonergic agonists, suggesting that the receptors mediating serotonin-induced contractility in these tissues were similar. In addition, the contractile potency (estimated as EC50 values) for these structurally diverse serotonergic agonists in either the rabbit or canine saphenous vein significantly correlated with contractile potency for these agonists in human cerebral arteries. Thus, to the extent that contractile responsiveness of human cerebral arteries may predict antimigraine agents, contractile responses of the rabbit and/or canine saphenous vein may be useful surrogates for antimigraine efficacy. In addition, the contractile potency for this series of serotonergic agonists in the rabbit or canine saphenous vein significantly correlated with contractile potency of these agonists in human coronary arteries. These data suggest that the use of the saphenous vein to identify potent vasoconstrictors will also reveal agents capable of contracting human coronary arteries, a liability for using this approach to evaluate promising antimigraine therapies.
Cohen
M L
ML
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, USA.
Johnson
K W
KW
Schenck
K W
KW
Phebus
L A
LA
D000818:Animals; D002536:Cerebral Arteries / Q000187:drug effects* / Q000378:metabolism; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D006801:Humans; D008881:Migraine Disorders / Q000188:drug therapy*; D011817:Rabbits; D011985:Receptors, Serotonin / Q000187:drug effects*; D012501:Saphenous Vein / Q000187:drug effects* / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects*
D011985:Receptors, Serotonin