Effects of U-40481 and formetanate on the isolated rabbit central ear artery

Formetanate, a formamidine-type pesticide, and U-40481 (N-methyl-N′-2,4-xylylformamidine), a metabolite of amitraz, also a formamidine pesticide, contract the rabbit central ear artery with their maximal contractions being 22 ± 8% and 49 ± 6% of norepinephrine contractions, respectively. Maximal contractions were obtained with 10^?3M formetanate and 10^?4M U-40481, and cumulatively added higher concentrations caused a decrease in tension from that maximum. Their contractions were antagonized by 10^?6M and 3 × 10^?6M phentolamine. U-40481 reversibly antagonized contractions induced by serotonin, norepinephrine, and histamine, and to some extent potassium. Formetanate had little antagonist activity. Neither compound altered the resting rate of washout of radioactivity from ³H]norepinephrine preloaded strips. Both reduced electrically induced release, which may be related to local anesthetic-like actions on sympathetic neurones. Thus both compounds are partial agonists at the α-adrenergic receptor, and reduce electrically induced norepinephrine release, and U-40481 antagonizes contractions induced by certain other vasoactive agents.