[Effects of dihydroergotamine mesylate (DEM) on the cardiovascular and nervous systems (author's transl)].

Effects of DEM on the cardiovascular, autonomic, and central nervous systems were studied using dogs, rats and rabbits. DEM showed relatively weak effects on the EEG in curarized rabbits and on ambulatory and drinking activities in rats. DEM suppressed dose-dependently the pressor responses induced by norepinephrine, serotonin and bilateral carotid occlusion, but had no effect on the depressor responses induced by acetylcholine and electrical stimulation to the postganglionic vagus nerve in anesthetized dogs. DEM produced a dose-dependent increase in blood pressure, a dose-dependent decrease in heart rate, a transient decrease in respiration rate, and little change in the ECG of anesthetized dogs. The pressor responses induced by DEM were inhibited by phentolamine, methysergide, and indomethacin in anesthetized dogs. With canine femoral arteries, DEM-induced contractions were blocked 10% by phentolamine, 60% by methysergide, and enhanced 10% by indomethacin. On the other hand, DEM-induced contractions of the femoral veins were blocked 30% by phentolamine, 60% by indomethacin, and 10% by methysergide. DEM provoked a significant increase in the level of prostaglandin E in the bathing fluid of the veins but not in that of the arteries. The results suggest that the arterioconstrictor responses induced by DEM are mediated mainly through the serotonin receptors, and the venoconstrictor responses induced by DEM mainly through the enhanced synthesis of prostaglandin E.