Nickel B, Schulze G, Szelenyi I
Department of Pharmacology, ASTA Pharma AG, Frankfurt/Main, F.R.G.
Neuropharmacology. 1990 Nov;29(11):983-92. doi: 10.1016/0028-3908(90)90103-x.
In the present study, whether the repeated administration of (-)deprenyl to rats resulted in physical dependency was investigated. In a second experiment, the effect of (-)-deprenyl was investigated on the cortical electrical activity of freely moving rats and last, the influence of (-)-deprenyl on the behaviour of the animals was studied. In all experiments, different stereospecific configurations of amphetamine and deprenyl were also employed in order to establish differences and similarities. During and after the chronic oral administration of (-)-deprenyl (4 mg/kg) over 6 weeks, no signs of physical dependency were observed in rats after withdrawal of the drug. By contrast, (+)-deprenyl (5 mg/kg, p.o.) and (+)-amphetamine (5 mg/kg, p.o.) induced typical symptoms of amphetamine-dependency: during withdrawal of drug, the body weight of the rats was increased. A similar phenomenon was observed after oral administration of (+/-)-amphetamine (6 mg/kg, p.o.). After a single oral administration of (-)-deprenyl (1 and 5 mg/kg) and (-)-amphetamine (10 mg/kg, p.o.), decreases in delta and increases in theta frequency bands in the EEG were observed. In contrast, (+)-amphetamine (1 mg/kg, p.o.), (+/-)-amphetamine (5 mg/kg, p.o.) and (+)-deprenyl (1 and 5 mg/kg, p.o.) evoked increases in the mean power values in delta and decreases in theta frequency bands. In agreement with the EEG studies, the (-) and (+)-isomers of amphetamine and deprenyl caused differences in the behaviour of the animals. Based on these findings, it can be concluded that (-)-deprenyl undergoes a stereospecific metabolism in the organism and the amounts of its metabolites with (+) configuration might be negligible, even at the larger doses which are necessary to inhibit monoamine oxidase-B (MAOB) in brain.
在本研究中，调查了对大鼠重复给予（-）司来吉兰是否会导致身体依赖性。在第二个实验中，研究了（-）-司来吉兰对自由活动大鼠皮质电活动的影响，最后，研究了（-）-司来吉兰对动物行为的影响。在所有实验中，还使用了苯丙胺和司来吉兰的不同立体特异性构型，以确定差异和相似之处。在对大鼠进行为期6周的慢性口服（-）-司来吉兰（4mg/kg）期间及之后，停药后未观察到大鼠有身体依赖性的迹象。相比之下，（+）-司来吉兰（5mg/kg，口服）和（+）-苯丙胺（5mg/kg，口服）诱发了典型的苯丙胺依赖性症状：在停药期间，大鼠体重增加。口服（±）-苯丙胺（6mg/kg，口服）后也观察到类似现象。单次口服（-）-司来吉兰（1mg/kg和5mg/kg）和（-）-苯丙胺（10mg/kg，口服）后，脑电图中δ波减少，θ波频段增加。相比之下，（+）-苯丙胺（1mg/kg，口服）、（±）-苯丙胺（5mg/kg，口服）和（+）-司来吉兰（1mg/kg和5mg/kg，口服）诱发δ波平均功率值增加，θ波频段减少。与脑电图研究一致，苯丙胺和司来吉兰的（-）和（+）异构体在动物行为上产生了差异。基于这些发现，可以得出结论，（-）-司来吉兰在生物体内经历立体特异性代谢，即使在抑制脑内单胺氧化酶-B（MAOB）所需的较大剂量下，其具有（+）构型的代谢产物量可能也可忽略不计。
