Peroutka S J, Gonzales D A, Shapiro M
Exp Neurol. 1987 May;96(2):344-51. doi: 10.1016/0014-4886(87)90052-5.
Postdecapitation convulsions were analyzed in rats after the administration of a variety of adrenergic and serotonergic agents. Drugs were selected on the basis of their relative affinities for 5-hydroxytryptamine1A, alpha 2-adrenergic and/or alpha 1-adrenergic receptors. The 5-hydroxytryptamine1A-selective agonists, 8-hydroxy-N,N-dipropyl-2-aminotetralin and buspirone, significantly increased the duration of the convulsions. The alpha 2-adrenergic antagonists, yohimbine and corynanthine, had no affect on either the latency or duration of the convulsions. By contrast, each of the three alpha 1-adrenergic agents increased the latency and decreased their duration. However, the order of potency was WB 4101 greater than ipsapirone greater than prazosin and this rank order did not correlate with drug potencies for the alpha 1-adrenergic receptor as determined by radioligand binding studies. The high potency of both ipsapirone and WB 4101 in inhibiting the postdecapitation convulsions may relate to the combined effects of the drugs at both alpha 1-adrenergic and 5-hydroxytryptamine1A receptors.
在给大鼠施用多种肾上腺素能和血清素能药物后,对断头后惊厥进行了分析。根据药物对5-羟色胺1A、α2-肾上腺素能和/或α1-肾上腺素能受体的相对亲和力来选择药物。5-羟色胺1A选择性激动剂8-羟基-N,N-二丙基-2-氨基四氢萘和丁螺环酮显著增加了惊厥的持续时间。α2-肾上腺素能拮抗剂育亨宾和柯楠碱对惊厥的潜伏期或持续时间均无影响。相比之下,三种α1-肾上腺素能药物中的每一种都增加了潜伏期并缩短了其持续时间。然而,效力顺序为WB 4101大于伊沙匹隆大于哌唑嗪,且这种排序与通过放射性配体结合研究确定的α1-肾上腺素能受体的药物效力不相关。伊沙匹隆和WB 4101在抑制断头后惊厥方面的高效力可能与药物在α1-肾上腺素能和5-羟色胺1A受体上的联合作用有关。