Effects of the Novel Antimigraine Agent, Frovatriptan, on Coronary and Cardiac Function in Dogs

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Abstract
The effects of frovatriptan (VML 251/SB-209509) on coronary artery function were investigated in isolated coronary arteries from beagle dogs. Low concentrations of frovatriptan produced contraction with -logEC50 7.55 ± 0.08 (n = 11). The maximal observed contraction attained was 56 ± 7% of the control 5-hydroxytryptamine (5-HT; 10 μM) response. At high concentrations of frovatriptan (>6 μM), reversal of sumatriptan (10 μM)-induced contractions was noted. In arteries precontracted with the thromboxane mimetic, U46619, frovatriptan produced a bell-shaped concentration-response relation with a maximal response at 600 nM. Concentrations of frovatriptan >2 μM produced marked reversal of tone, with full relaxation of precontracted tissues at 200 μM. In anesthetized, open-chest mongrel dogs, intravenous (n = 5) or intracoronary (n = 5) artery administration of frovatriptan (0.0001-1 mg/kg) had no consistent effect on left ventricular end-diastolic pressure, left end-systolic pressure, cardiac contractility, aortic blood flow, systemic peripheral resistance, coronary blood flow, coronary vascular resistance, mean arterial blood pressure, or heart rate when compared with vehicle (n = 3). Intravenous sumatriptan produced minor effects on blood pressure and heart rate. Intracoronary artery administration of sumatriptan (0.0003 mg/kg) produced an increase in systemic peripheral resistance to 120.5 ± 8.2% compared with vehicle (97.8 ± 5.4%; p

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