Cardiovascular responses to combined treatment with selective monoamine oxidase type B inhibitors and L‐DOPA in the rat

Background and purpose: Postural hypotension is a common side‐effect of L‐DOPA treatment of Parkinson's disease, and may be potentiated when L‐DOPA is combined with selegiline, a selective inhibitor of monoamine oxidase B (MAO‐B). Rasagiline is a new, potent and selective MAO‐B inhibitor, which...

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Published in:British journal of pharmacology 2006-11, Vol.149 (6), p.647-656
Main Authors: Finberg, J P M, Gross, A, Bar‐Am, O, Friedman, R, Loboda, Y, Youdim, M B H
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
blood pressure
Blood Pressure - drug effects
carbidopa
clorgyline
heart rate
Heart Rate - drug effects
Levodopa - pharmacology
L‐DOPA
Male
Medical sciences
Monoamine Oxidase - drug effects
Monoamine Oxidase Inhibitors - pharmacology
Pharmacology. Drug treatments
rasagiline
Rats
Rats, Sprague-Dawley
Research Papers
selegiline
tranylcypromine
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Summary:Background and purpose: Postural hypotension is a common side‐effect of L‐DOPA treatment of Parkinson's disease, and may be potentiated when L‐DOPA is combined with selegiline, a selective inhibitor of monoamine oxidase B (MAO‐B). Rasagiline is a new, potent and selective MAO‐B inhibitor, which does not possess the sympathomimetic effects of selegiline. We have studied the effects of these selective MAO inhibitors, L‐DOPA and dopamine on the cardiovascular system of the rat. Experimental approach: Blood pressure and heart rate was measured in conscious rats following acute or chronic administration of rasagiline, selegiline and L‐DOPA, by comparison with the selective MAO‐A inhibitor clorgyline, or the MAO‐A/B inhibitor tranylcypromine. Cardiovascular responses, catecholamine release, and modification of pressor response to dopamine were studied in pithed rats. Key results: In conscious rats neither rasagiline nor selegiline caused significant potentiation of the effects of L‐DOPA (50, 100, 150 mg.kg−1) on blood pressure or heart rate at doses which selectively inhibited MAO‐B, but L‐DOPA responses were potentiated by clorgyline and tranylcypromine. In rats treated twice daily for 8 days with L‐DOPA and carbidopa, selegiline (5 mg.kg−1) but not rasagiline (0.2 mg.kg−1) caused a significant hypotensive response to L‐DOPA and carbidopa, although both drugs caused similar inhibition of MAO‐A and MAO‐B. In pithed rats, selegiline but not rasagiline increased catecholamine release and heart rate, and potentiated dopamine pressor response at MAO‐B selective dose. Conclusions and implications: The different responses to the two MAO‐B inhibitors may be explained by the amine releasing effect of amphetamine metabolites formed from selegiline. British Journal of Pharmacology (2006) 149, 647–656. doi:10.1038/sj.bjp.0706908
ISSN:0007-1188
1476-5381
DOI:10.1038/sj.bjp.0706908