Pericić D, Mück-Seler D
Department of Experimental Biology and Medicine, Rudjer Bosković Institute, Zagreb, Yugoslavia.
Life Sci. 1990;46(19):1331-42. doi: 10.1016/0024-3205(90)90332-l.
The mechanisms by which imipramine and dihydroergosine stimulate the 5-HT syndrome in rats and inhibit the head-twitch response in rats and mice were studied. Imipramine- and dihydroergosine-induced stimulation of the 5-HT syndrome was inhibited stereoselectively by propranolol, a high affinity ligand for 5-HT1 receptor sites, but not by ritanserin, a specific 5-HT2 receptor antagonist. (-)-Propranolol potentiated the inhibitory effect of imipramine, but not of dihydroergosine on the head-twitch response, while ritanserin was without effect. Neither imipramine nor dihydroergosine were able to stimulate the 5-HT syndrome in the animals pretreated with p-chlorophenylalanine. As expected, 8-OH-DPAT, a selective 5-HT1A receptor agonist, stimulated, and 5-HT1B agonists CGS 12066B and 1-(trifluoromethylphenyl)piperazine (TFMPP) failed to stimulate the 5-HT syndrome induced in rats by pargyline and 5-HTP administration. A higher dose of ritanserin inhibited the syndrome. While 8-OH-DPAT alone produced all behavioral components of the 5-HT syndrome, dihydroergosine or imipramine alone even at very high doses never produced tremor or a more intensive forepaw padding as seen when these drugs were given in combination with pargyline and 5-HTP. A single administration of (-)-propranolol also inhibited the head-twitch response. This effect lasted in mice longer than after ritanserin administration. In in vitro experiments dihydroergosine expressed approximately twenty-fold higher affinity for 3H-ketanserin binding sites than imipramine. The results suggest that imipramine and dihydroergosine possess two components--one stimulating the 5-HT syndrome in rats by a presynaptic, presumably 5-HT1A-mediated mechanism, and the other inhibiting 5-HT2 binding sites.
研究了丙咪嗪和双氢麦角隐亭刺激大鼠5-羟色胺（5-HT）综合征以及抑制大鼠和小鼠头部抽搐反应的机制。5-HT1受体位点的高亲和力配体普萘洛尔能立体选择性地抑制丙咪嗪和双氢麦角隐亭诱导的5-HT综合征，但5-HT2特异性受体拮抗剂利坦色林则无此作用。（-）-普萘洛尔增强了丙咪嗪对头部抽搐反应的抑制作用，但对双氢麦角隐亭无此作用，而利坦色林则无效。在用对氯苯丙氨酸预处理的动物中，丙咪嗪和双氢麦角隐亭均不能刺激5-HT综合征。正如预期的那样，选择性5-HT1A受体激动剂8-OH-DPAT能刺激5-HT综合征，而5-HT1B激动剂CGS 12066B和1-（三氟甲基苯基）哌嗪（TFMPP）不能刺激由帕吉林和5-羟色氨酸诱导的大鼠5-HT综合征。高剂量的利坦色林能抑制该综合征。虽然单独使用8-OH-DPAT能产生5-HT综合征的所有行为成分，但单独使用双氢麦角隐亭或丙咪嗪，即使剂量很高，也不会产生震颤或比与帕吉林和5-羟色氨酸联合使用时更强烈的前爪拍打。单次给予（-）-普萘洛尔也能抑制头部抽搐反应。这种作用在小鼠体内持续的时间比利坦色林给药后更长。在体外实验中，双氢麦角隐亭对3H-酮色林结合位点的亲和力比对丙咪嗪高约20倍。结果表明，丙咪嗪和双氢麦角隐亭具有两种作用机制——一种通过突触前机制（可能是5-HT1A介导）刺激大鼠的5-HT综合征，另一种则抑制5-HT2结合位点。
