Perrone M H, Hamel L T, Ferrari R A, Haubrich D R
Department of Pharmacology, Sterling Research Group, Rensselaer, New York.
J Pharmacol Exp Ther. 1990 Aug;254(2):471-5.
Napamezole (2-[3,4-dihydro-2-naphthalenyl)methyl]-4,5-dihydro-1H- imidazole-monohydrochloride) is a selective alpha-2 adrenergic receptor antagonist and a monoamine re-uptake inhibitor in vitro. The alpha adrenergic antagonist activity of napamezole was determined in vitro in rat brain receptor binding assay using [3H]clonidine and [3H]prazosin for alpha-2 and alpha-1 receptors, respectively. The Ki values for napamezole were 28 nM (alpha-2) and 93 nM (alpha-1). The relative potencies for inhibiting [3H]clonidine binding were: phentolamine greater than idazoxan greater than napamezole greater than mianserin greater than yohimbine greater than piperoxan greater than rauwolscine greater than tolazoline much greater than prazosin; and for inhibition [3H]prazosin binding they were: prazosin greater than phentolamine greater than mianserin greater than napamezole greater than yohimbine greater than idazoxan greater than tolazoline. Alpha adrenoceptor antagonism was also assessed in the isolated rat vas deferens. Napamezole reversed clonidine-induced decreased in twitch height in the electrically stimulated rat vas deferens (alpha-2 antagonism with a Kb of 17 nM). The rank order of potency as an alpha-2 antagonist relative to other compounds was phentolamine greater than idazoxan greater than yohimbine greater than piperoxan = napamezole greater than mianserin much greater than prazosin. Napamezole also antagonized methoxamine-induced contractions (alpha-1) of the rat vas deferens with a Kb of 135 nM. The rank order of potency of these compounds as alpha-1 antagonists was prazosin greater than phentolamine greater than mianserin greater than yohimbine greater than napamezole greater than idazoxan.(ABSTRACT TRUNCATED AT 250 WORDS)
萘哌咪唑（2 - [3,4 - 二氢 - 2 - 萘基）甲基] - 4,5 - 二氢 - 1H - 咪唑 - 盐酸盐）在体外是一种选择性α - 2肾上腺素能受体拮抗剂和单胺再摄取抑制剂。萘哌咪唑的α肾上腺素能拮抗剂活性在体外大鼠脑受体结合试验中测定，分别使用[³H]可乐定和[³H]哌唑嗪检测α - 2和α - 1受体。萘哌咪唑的Ki值分别为28 nM（α - 2）和93 nM（α - 1）。抑制[³H]可乐定结合的相对效价顺序为：酚妥拉明＞伊达唑胺＞萘哌咪唑＞米安色林＞育亨宾＞哌泊昔生＞萝芙辛＞妥拉唑啉＞哌唑嗪；抑制[³H]哌唑嗪结合的相对效价顺序为：哌唑嗪＞酚妥拉明＞米安色林＞萘哌咪唑＞育亨宾＞伊达唑胺＞妥拉唑啉。α肾上腺素能受体拮抗作用也在离体大鼠输精管中进行了评估。萘哌咪唑可逆转可乐定引起的电刺激大鼠输精管抽搐高度降低（α - 2拮抗作用，Kb为17 nM）。相对于其他化合物，作为α - 2拮抗剂的效价顺序为：酚妥拉明＞伊达唑胺＞育亨宾＞哌泊昔生 = 萘哌咪唑＞米安色林＞哌唑嗪。萘哌咪唑还拮抗甲氧明引起的大鼠输精管收缩（α - 1），Kb为135 nM。这些化合物作为α - 1拮抗剂的效价顺序为：哌唑嗪＞酚妥拉明＞米安色林＞育亨宾＞萘哌咪唑＞伊达唑胺。（摘要截选至250字）
