Rasagiline enhances L-DOPA-induced contralateral turning in the unilateral 6-hydroxydopamine-lesioned guinea-pig
by
Moses D, Gross A, Finberg JP.
Pharmacology Department,
Rappaport Family Faculty of Medicine,
Technion, P.O. Box 9649,
31096 Haifa, Israel.
Neuropharmacology. 2004 Jul;47(1):72-80

ABSTRACT

The modification of L-3,4-dihydrooxyphenylalanine- (L-DOPA-) induced turning response by the new selective monoamine oxidase type B (MAO-B) inhibitor rasagiline was studied in guinea-pigs bearing a unilateral 6-hydroxydopamine-induced lesion in the substantia nigra. In an initial experiment, it was established that contralateral turning is induced in lesioned guinea-pigs in response to apomorphine (18 mg/kg i.p.) and L-DOPA/carbidopa (15/3.5 mg/kg i.p.), while ipsilateral turning is induced by S(+)-methamphetamine (7 mg/kg i.p.). The effect of rasagiline was studied in a chronic treatment regimen, in which animals were treated with rasagiline (0.05 mg/kg s.c.) or saline s.c. daily commencing 2 weeks after lesioning, and L-DOPA/carbidopa (4:1 mg/kg) was administered once daily for 21 days. Only guinea-pigs with 95% or more depletion of striatal dopamine were included in this study. Guinea-pigs treated with rasagiline had a significantly increased intensity and duration of turning in response to L-DOPA (P <0.05 by repeated measures ANOVA) over the 21-day period. On day 21, turning averaged 806+/-105 (n=10) vs 442+/-123 (n=11) turns per 180 min for rasagiline and vehicle treated animals, respectively (P <0.05); turning duration half-time averaged 81+/-15.4 (n=10) as opposed to 33+/-7.6 (n=11) min for rasagiline and vehicle treatments (P <0.01). Concentration of dopamine in intact striatum was significantly increased (69.3+/-2.1 and 60.3+/-2.4 pmol/mg tissue for rasagiline and vehicle, P <0.05) and levels of dihydroxyphenylacetic acid and homovanillic acid were decreased by the rasagiline treatment. Activity of brain MAO-B was 8.6+/-2.9% and MAO-A was 71+/-1.5% that of control in rasagiline-treated animals. Chronic, selective inhibition of MAO-B by rasagiline potentiated L-DOPA-induced turning in this rodent model.

L-DOPA
Parkinson's disease
Dopamine cell death
Rasagiline: structure
MAO-b inhibitors/PD
Anti-apoptotic activity
Molecular mechanisms
Rasagiline pharmacology
The introduction of L-DOPA
Induction of pro-survival genes
Rasagiline and the mitochondria
Antioxidant strategies against aging
Anti-Alzheimer/anti-Parkinson's drugs
Rasagiline versus selegiline metabolites

Refs
and further reading

HOME
HedWeb
Nootropics
cocaine.wiki
Future Opioids
BLTC Research
MDMA/Ecstasy
Superhapiness?
Utopian Surgery?
The Abolitionist Project
The Hedonistic Imperative
The Reproductive Revolution
Critique of Huxley's Brave New World

The Good Drug Guide
The Responsible Parent's Guide
To Healthy Mood Boosters For All The Family