The neuroprotective mechanism of 1‐(R)‐aminoindan, the major metabolite of the anti‐parkinsonian drug rasagiline

Abstract

J. Neurochem. (2010) 112, 1131–1137. Abstract The anti‐parkinsonian drug, rasagiline [N‐propargyl‐1‐(R)‐aminoindan; Azilect®], is a secondary cyclic benzylamine and indane derivative, which provides irreversible, potent monoamine oxidase‐B (MAO‐B) inhibition and possesses neuroprotective and neurorestorative activities. A prospective clinical trial has shown that rasagiline confers significant symptomatic improvement and demonstrated alterations in Parkinson’s disease progression. Rasagiline is primarily metabolized by hepatic cytochrome P‐450 to form its major metabolite, 1‐(R)‐aminoindan, a non‐amphetamine, weak reversible MAO‐B inhibitor compound. Recent studies indicated the potential neuroprotective effect of 1‐(R)‐aminoindan, suggesting that it may contribute to the overall neuroprotective and antiapoptotic effects of its parent compound, rasagiline. This review article briefly highlights the molecular mechanisms underlying the neuroprotective properties of the active metabolite of rasagiline, 1‐(R)‐aminoindan, supporting the valuable potential of rasagiline for disease modification.

Rasagiline: A Review of Its Use in the Treatment of Idiopathic Parkinson’s Disease

“…The major metabolites of N-dealkylation and/or hydroxylation are l-aminoindan, 3-hydroxy-N-propargyl-l-aminoindan and 3-hydroxy-l-aminoindan; biotransformation is virtually complete [5]. These metabolites do not inhibit MAO-B, but the major metabolite 1-aminoindan has neuroprotective properties that may contribute to the overall neuroprotective activity of rasagiline [12,23]. The major elimination pathway is urinary excretion of glucuronide conjugates of rasagiline and its metabolites.…”

Selegiline rescues gait deficits and the loss of dopaminergic neurons in a subacute MPTP mouse model of Parkinson’s disease

“…Monoamine oxidase type-B (MAO-B) inhibitors have returned to the spotlight as an alternative to dopaminergic replacement therapy and studies have demonstrated that they enhance cognitive function (2) and exert neuroprotective effects (3). Disease modification has also been investigated in previous studies, assessing the effects of the MAO-B inhibitors, selegiline and rasagiline (3,4). Although selegiline, the first selective inhibitor of MAO-B, has been widely used in patients with PD as monotherapy and adjuvant therapy, its basic and clinical pharmacological effects have not yet been fully elucidated.…”

Pathogenesis-Targeted, Disease-Modifying Therapies in Parkinson Disease

“…Rasagiline is a newer propargylamine derivative and more potent MAO-B inhibitor than selegiline. Some reports also suggest that the aminoindan metabolite of rasagiline confer additional neuroprotective activity [9]. Rasagiline has been studied using a delayed-start clinical trial design intended to reduce the confounding effect of symptomatic efficacy.…”