• YAKHAK HOEJI
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• v.43 no.1
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• pp.33-41
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• 1999

Whereas as selective inhibitor of monoamine oxidase type B, ${\ell}-deprenyl$ (selegiline), is now widely used in the treatment of Parkinson's disease, the precise action mechanism of the drug remains elusive. In this study, to investigate protective effect of ${\ell}-deprenyl$ against the dopamine depletion induced by 6-hydroxydopamine (6-OHDA), the changes in tissue contents of dopamine, serotonine (5-HT) and their metabolites by ${\ell}-deprenyl$ were examined in intact and 6-OHDA-lesioned rat brain. In intact rats, a single intraperitoneal (i.p.) administration of ${\ell}-deprenyl$ showed a no change in striatal dopamine and its metabolites at low concentrations (0.25 and 1 mg/kg), but significantly inhibited dopamine metabolism at a higher concentration (10 mg/kg). The repeated administration of ${\ell}-deprenyl$ (0.25 and 1 mg/kg, i.p., for 21 consecutive days) reduced the contents of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanilic acid (HVA) in dose-dependent manners without changes in dopamine content. Bilateral intracerebroventricular (i.c.v) infusion of 6-OHDA ($100{\;}\mu\textrm{g}/10{\;}{\mu}{\ell}/hemisphere$) depleted dopamine in striatum and septum by 81% and 90% respectively. When rats were pretreated with ${\ell}-deprenyl$ before 6-OHDA administration, the striatal and septal dopamine levels were significantly increased by about 3.0-fold and 3.4-fold, respectively, compared to the untreated 6-OHDA-lesioned rat. Pretreatment of ${\ell}-deprenyl$ also significantly enhanced the dopmaine metabolites, DOPAC, HVA and 3-methoxytyramine, in the striatum, and DOPAC in the septum. These results indicate that a ${\ell}-deprenyl$ pretreatment prevents 6-OHDA-induced depletion of striatal dopamine and its metabolites.

• YAKHAK HOEJI
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• v.42 no.1
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• pp.101-107
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• 1998

The antiparkinsonian agent l-deprenyl, a selective monoamine oxidase (MAO)-B inhibitor, is metabolized in part to l-methamphetamine and l-amphetamine. l< /I>-Deprenyl was evaluated for amphetamine and methamphetamine-like discriminative stimulus effects in rats and its mechanism of action was investigated. Rats were trained under a 5-response, fixed ratio schedule of stimulus-shock termination or a 10-response. Fixed-ratio schedule of food-presentation which discriminate between d-amphetamine (1mg/kg, i.p.) and saline or d-methamphetamine (1mg/kg, i.p.) and saline in a two-lever, operant conditioning procedure. Full generalization was obtained to d-amphetamine (1~3mg/kg). d-methamphetamine (1~3mg/kg) and l-deprenyl (17~30mg/kg) under both the food presentation and stimulus shock termination schedule. l-Deprenyl has dose-dependent amphetamine-and methamphetamine-like discriminative stimulus properties in rats only at doses of 17 and 30mg/kg. Reversible MAO-B inhibitor, RO 16-6491 didn`t show any amphetamine-like discriminative properties. Aromatic amino acid decarboxylase inhibitor, NSD 1015 decreased % responding of l-deprenyl in the methamphetamine-trained rats under the stimulus-shock termination schedule. SKF-525A produced partial inhibition of methamphetamine-like discriminative effects of l-deprenyl under the food presentation schedule. These results suggest that l-deprenyl has no abuse liability at the therapeutic range but there needs some caution at high doses and furthermore, drug discrimination studies under the food presentation and shock termination schedule are useful for the assessment of abuse liability of psychostimulants.

• YAKHAK HOEJI
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• v.41 no.6
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• pp.698-703
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• 1997

Recently, l-deprenyl (selegiline), a relative new antiparkinson`s drug, has been marketed in Korea. As its metabolites, l-methamphetamine and l-amphetamine, are the enantiomers of illicit drugs,d-methamphetamine and d-amphetamine, a method for analysis of enantiomers of methamphetamine and amphetamine in rat urine was investigated. The optical isomers of methamphetamine and amphetamine were analyzed with the chiral derivatizing reagent (S)-(-)-N-(trifluoroacetyl)-prolyl chloride (l-TFP), which was used to form the diastereomers of methamphetamine and amphetamine. And all diastereomers (l-TFP -l-AM, lTFP-d-AM, l-TFP-l-MA & l-TFP-d-MA) were well resolved by capillary gas chromatography. After administration of 10mg/kg l-deprenyl to rat, l-methamphetamine and l-amphetamine were detected without autoracemization to the d form in all urine samples collected during 24hrs, and the ratios of l-amphetamine/l-methamphetamine were 1.1~3.3. l-Amphetamine was detected in only 3 out of 8 urine samples collected during 24~48hrs where as no l-methamphetamine was detected in all cases.