From the Department of Pharmacology, Erasmus University Rotterdam, and
Department of Neurology (M.D.F.), Leiden University Medical Centre, the
Netherlands. Dr Bax is now with the Department of Cardiology and Internal
Medicine, Eemland Hospital, Amersfoort, the Netherlands.
Correspondence to P.R. Saxena, MD, PhD, Department of Pharmacology, Erasmus University Rotterdam, Dr Molewaterplein 50, PO Box 1738, 3000 DR Rotterdam, Netherlands. E-mail saxena{at}farma.fgg.eur.nl
Background—The antimigraine drugs
ergotamine and sumatriptan may cause angina-like symptoms, possibly
resulting from coronary artery constriction. We compared the
coronary vasoconstrictor potential of a number of current and
prospective antimigraine drugs (ergotamine, dihydroergotamine,
methysergide and its metabolite methylergometrine, sumatriptan,
naratriptan, zolmitriptan, rizatriptan, avitriptan).
Methods and Results—Concentration-response curves to the
antimigraine drugs were constructed in human isolated coronary
artery segments to obtain the maximum contractile response
(Emax) and the concentration eliciting 50% of
Emax (EC50). The EC50 values were
related to maximum plasma concentrations (Cmax) reported in
patients, obtaining Cmax/EC50 ratios as an
index of coronary vasoconstriction occurring in the clinical
setting. Furthermore, we studied the duration of contractile responses
after washout of the acutely acting antimigraine drugs to assess their
disappearance from the receptor biophase. Compared with sumatriptan,
all drugs were more potent (lower EC50 values) in
contracting the coronary artery but had similar efficacies
(Emax <25% of K+-induced contraction). The
Cmax 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 declined rapidly after
washing.
Conclusions—All current and prospective antimigraine drugs
contract the human coronary artery in vitro, but in view of low
efficacy, these drugs are unlikely to cause myocardial ischemia
at therapeutic plasma concentrations in healthy subjects. In patients
with coronary artery disease, however, these drugs must remain
contraindicated. The sustained contraction by ergotamine and
dihydroergotamine seems to be an important disadvantage compared with
sumatriptan-like drugs.
© 1998 American Heart Association, Inc.
Clinical Investigation and Reports
Coronary Side-Effect Potential of Current and Prospective Antimigraine Drugs
Key Words: coronary disease • vasoconstriction • migraine • pharmacology • antimigraine drugs
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