Kachur J F, Allbee W E, Gaginella T S
NOVA Pharmacentical Corp., Baltimore, Maryland.
J Pharmacol Exp Ther. 1988 May;245(2):455-9.
Amitriptyline, a tricyclic antidepressant, was tested for antimuscarinic and antihistamine effects against bethanechol and histamine-stimulated contractility and secretion in the guinea pig ileum in vitro. Comparisons were made with muscarinic-receptor antagonists, as well as with H1 and H2 histamine-receptor antagonists. Amitriptyline (0.01-5.0 microM) produced a parallel rightward shift in the concentration-response curves to histamine in muscle (Ki 0.4 nM) and mucosa (Ki 450 nM). The H1-receptor antagonists pyrilamine and diphenhydramine were less potent against histamine in the muscle and more potent against histamine in the mucosa than was amitriptyline. The H2-receptor antagonist cimetidine was ineffective in the muscle and mucosa. Amitriptyline (0.1-2 microM) also produced a parallel rightward shift in the concentration-response curve to bethanechol in muscle (Ki 133 nM) and mucosa (Ki 143 nM). Against bethanechol, in both tissues, atropine and 4-diphenylacetoxy-N-methyl piperidine methiodide were more potent competitive antagonists than was amitriptyline. Pirenzepine produced a competitive blockade of bethanechol in the muscle and a noncompetitive blockade in the mucosa. The data indicate that amitriptyline exerts more potent antihistaminic effects on guinea pig ileal muscle than the mucosa but that the tricyclic drug is equipotent as an antimuscarinic in both tissues.
对三环类抗抑郁药阿米替林进行了测试，观察其对豚鼠离体回肠中由氨甲酰甲胆碱和组胺刺激引起的收缩性和分泌的抗毒蕈碱和抗组胺作用。将其与毒蕈碱受体拮抗剂以及H1和H2组胺受体拮抗剂进行了比较。阿米替林（0.01 - 5.0微摩尔）使肌肉（Ki 0.4纳摩尔）和黏膜（Ki 450纳摩尔）中组胺浓度 - 反应曲线平行右移。H1受体拮抗剂吡苄明和苯海拉明在肌肉中对组胺的作用不如阿米替林有效，而在黏膜中对组胺的作用比阿米替林更强。H2受体拮抗剂西咪替丁在肌肉和黏膜中均无作用。阿米替林（0.1 - 2微摩尔）也使肌肉（Ki 133纳摩尔）和黏膜（Ki 143纳摩尔）中氨甲酰甲胆碱浓度 - 反应曲线平行右移。在两种组织中，与阿米替林相比，阿托品和4 - 二苯乙酰氧基 - N - 甲基哌啶甲碘化物作为氨甲酰甲胆碱的竞争性拮抗剂作用更强。哌仑西平在肌肉中对氨甲酰甲胆碱产生竞争性阻断，在黏膜中产生非竞争性阻断。数据表明，阿米替林对豚鼠回肠肌肉的抗组胺作用比对黏膜更强，但这种三环类药物在两种组织中作为抗毒蕈碱药的效力相当。
