CORONARY SIDE-EFFECT POTENTIAL OF CURRENT AND PROSPECTIVE ANTIMIGRAINE DRUGS

Background-The antimigraine drugs ergotamine and sumatriptan may cause angina-like symptoms, possibly resulting from coronary artery constri ction. We compared the coronary vasoconstrictor potential of a number of current and prospective antimigraine drugs (ergotamine, dihydroergo tamine, methysergide and its metabolite methylergometrine, sumatriptan , naratriptan, zolmitriptan, rizatriptan, avitriptan). Methods and Res ults-Concentration-response curves to the antimigraine drugs were cons tructed in human isolated coronary artery segments to obtain the maxim um contractile response (E-max) and the concentration eliciting 50% of E-max (EC50). The EC50 values were related to maximum plasma concentr ations (C-max) reported in patients, obtaining C-max/EC50 ratios as an index of coronary vasoconstriction occurring in the clinical setting. Furthermore, we studied the duration of contractile responses after w ashout of the acutely acting antimigraine drugs to assess their disapp earance from the receptor biophase. Compared with sumatriptan, all dru gs were more potent (lower EC50 values) in contracting the coronary ar tery but had similar efficacies (E-max <25% of K+-induced contraction) . The C-max of avitriptan was 7- to 11-fold higher than its EC50 value , whereas those of the other drugs were <40% of their respective EC50 values. The contractile responses to ergotamine and dihydroergotamine persisted even after repeated washings, but those to the other drugs d eclined rapidly after washing. Conclusions-All current and prospective antimigraine drugs contract the human coronary artery in vitro, but i n view of low efficacy, these drugs are unlikely to cause myocardial i schemia at therapeutic plasma concentrations in healthy subjects. In p atients with coronary artery disease, however, these drugs must remain contraindicated. The sustained contraction by ergotamine and dihydroe rgotamine seems to be an important disadvantage compared with sumatrip tan like drugs.