Effect of enantiomers of deprenyl (selegiline) and amphetamine on physical abuse liability and cortical electrical activity in rats.
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.
Nickel
B
B
Department of Pharmacology, ASTA Pharma AG, Frankfurt/Main, F.R.G.
Schulze
G
G
Szelenyi
I
I
D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology*; D003061:Codeine / Q000494:pharmacology; D004553:Electric Conductivity; D004569:Electroencephalography / Q000187:drug effects; D005071:Evoked Potentials / Q000187:drug effects; D005260:Female; D007536:Isomerism; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D012642:Selegiline / Q000494:pharmacology*; D013375:Substance Withdrawal Syndrome
D012642:Selegiline; D000661:Amphetamine; D003061:Codeine