Mutual inhibition and synergistic effects of ergotamine and the calcium antagonist darodipine.

The interaction between ergotamine 3 and 30 micrograms/kg i.v. and darodipine (PY108-068) 30 micrograms/kg i.v. was studied in anaesthetized cats. Ergotamine decreased heart rate, cardiac output and total peripheral conductance dose-dependently. Ergotamine caused regional vasoconstriction (measured with tracer microspheres) in the heart, kidneys, adrenals, liver, spleen, skin and arterio-venous shunts but dilatation in the pancreas and skeletal muscle, possibly attributable to serotoninergic stimulation. Darodipine reversed most ergotamine effects except those on the spleen, skin and arterio-venous shunts. Since constriction of arterio-venous shunts was not inhibited, ergotamine is unlikely to lose its effectiveness in migraine patients under concomitant dihydropyridine treatment, while unwanted vasoconstrictor effects are likely to be diminished.