Milgram N W, Ivy G O, Head E, Murphy M P, Wu P H, Ruehl W W, Yu P H, Durden D A, Davis B A, Paterson I A
Life Science Division, University of Toronto, Scarborough, Ontario, Canada.
Neurochem Res. 1993 Dec;18(12):1211-9. doi: 10.1007/BF00975038.
Behavioral and pharmacological effects of oral administration of L-deprenyl in the dog are described. Spontaneous behavior is unaffected at doses below 3 mg/kg while at higher doses there was stereotypical responding. There was evidence of improved cognitive function in animals chronically treated with a 1 mg/kg dose but the effectiveness varied considerably between subjects. Chronic administration produced a dose dependent inhibition in brain, kidney and liver monoamine oxidase B, and had no effect on monoamine oxidase A. There were also dose dependent increases in brain phenylethylamine and in plasma levels of amphetamine. Dog platelets did not have significant levels of MAO-B. Brain dopamine and serotonin metabolism were unaffected by L-deprenyl at doses up to 1 mg/kg. It appears that for the dog, deamination of catecholamines is controlled by MAO-A. Nevertheless, it is suggested that L-deprenyl serves as a dopaminergic agonist, and there is also evidence that it affects adrenergic transmission. These catecholaminergic actions may account for the effects of L-deprenyl on behavior and cognitive function.
描述了口服L-司来吉兰对犬的行为和药理作用。剂量低于3mg/kg时,自发行为不受影响,而剂量较高时会出现刻板反应。有证据表明,长期接受1mg/kg剂量治疗的动物认知功能有所改善,但不同个体之间的有效性差异很大。长期给药会对脑、肾和肝中的单胺氧化酶B产生剂量依赖性抑制,而对单胺氧化酶A没有影响。脑苯乙胺和血浆苯丙胺水平也有剂量依赖性升高。犬血小板中MAO-B的水平不显著。剂量高达1mg/kg时,L-司来吉兰对脑多巴胺和5-羟色胺代谢没有影响。对于犬来说,儿茶酚胺的脱氨基作用似乎由MAO-A控制。然而,有人认为L-司来吉兰可作为多巴胺能激动剂,也有证据表明它会影响肾上腺素能传递。这些儿茶酚胺能作用可能解释了L-司来吉兰对行为和认知功能的影响。