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

          recept

Bax, W.A. (Willem)

Ferrari, M.D. (Michel)

Maassen van den Brink, A. (Antoinette)

Reekers, M.

Saxena, P.R. (Pramod Ranjan)

Maassen van den Brink, Antoinette

Reekers, M

Bax, WA (Willem)

Ferrari, MD

Saxena, Pramod

NARCIS 

Coronary side-effect potential of current and prospective antimigraine drugs

EUR Research Repository

English


            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 (E
            max
            ) and the concentration eliciting 50% of E
            max
            (EC
            50
            ). The EC
            50
            values were related to maximum plasma concentrations (C
            max
            ) reported in patients, obtaining C
            max
            /EC
            50
            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 EC
            50
            values) in contracting the coronary artery but had similar efficacies (E
            max
            &lt;25% of K
            +
            -induced contraction). The C
            max
            of avitriptan was 7- to 11-fold higher than its EC
            50
            value, whereas those of the other drugs were &lt;40% of their respective EC
            50
            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.
          </jats:p

Antoinette MaassenVanDenBrink

Marije Reekers

Willem A. Bax

Michel D. Ferrari

Pramod R. Saxena

Crossref

Circulation

Coronary Side-Effect Potential of Current and Prospective Antimigraine Drugs

Undetermined

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

Erasmus University Digital Repository

Coronary side-effect potential of current and prospective antimigraine drugs

Abstract

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NARCIS

EUR Research Repository

Crossref

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Erasmus University Digital Repository