Cardiovascular activity of rasagiline, a selective and potent inhibitor of mitochondrial monoamine oxidase B: comparison with selegiline

1 Selegiline is used for treating Parkinson's disease. Despite its efficacy, the clinical use of selegiline in combination with L-dihydroxphenylalanine in Parkinsonian patients is hampered by cardiovascular complications, such as hypotension. This study was designed to compare in rats the cardiovascular effects of selegiline and rasagiline, their metabolites L-methamphetamine and aminoindan (TVP-136), respectively, and the second rasagiline metabolite non-monoamine oxidase (MAO) inhibitor TVP-1022 (N-propargyl-1S(-) aminoindan). 2 Intravenous (i.v.) administration of selegiline and rasagiline ( 1 mg kg(-1)) to anaesthetized rats ( thiobutabarbital, 100 mg kg(-1), i.p.) did not affect mean arterial pressure ( MAP), carotid blood flow (CBF) or carotid vascular resistance (CVR). Selegiline ( 10 mg kg(-1), i.v.) decreased MAP, CBF and increased CVR. In contrast, rasagiline (10 mg kg(-1), i.v.) caused a small transient decrease in MAP, while CBF and CVR were unchanged. 3 L-methamphetamine ( 1 mg kg(-1), i.v.) administration provoked a dramatic and long-lasting depressor response, decreased CBF and increased CVR. In contrast, injection of aminoindan or TVP-1022 at a similar dose produced gradual nonsignificant decreases in MAP and CBF. 4 Chronic oral treatment ( 21 days) of awake rats with selegiline at 10 mg kg(-1) decreased systolic blood pressure (SBP), diastolic blood pressure (DBP), and MAP, whereas heart rate was unaffected. Since the effective MAO-B inhibitory and clinical dose of rasagiline is about one-tenth that of selegiline, administration of 1 mg kg(-1) day(-1) rasagiline resulted in moderate decreases in SBP, DBP, and MAP, which were significantly lower than those caused by the 10 mg kg(-1) day(-1) dose of selegiline. 5 These findings indicate that rasagiline, when given at doses equivalent to selegiline, is less likely to be hypotensive.