Clinical Pharmacology of Rasagiline: A Novel, Second‐Generation Propargylamine for the Treatment of Parkinson Disease

Abstract

Rasagiline is a novel second-generation propargylamine that irreversibly and selectively inhibits monoamine oxidase type B (MAO-B). For the management of Parkinson disease (PD), rasagiline is efficacious across the span of PD stages ranging from monotherapy in early disease to adjunctive treatment in patients with advancing disease and motor fluctuations. Rasagiline completely and selectively inhibits MAO-B with a potency 5 to 10 times greater than selegiline. Unlike the prototype propargylamine selegiline, which is metabolized to amphetamine derivatives, rasagiline is biotransformed to aminoindan, a non-amphetamine compound. Rasagiline is well tolerated with infrequent cardiovascular or psychiatric side effects, and at the recommended therapeutic dose of up to 1 mg once daily, tyramine restriction is unnecessary. In addition to MAO-B inhibition, the propargylamine chain also confers dose-related antioxidant and antiapoptotic effects, which have been associated with neuroprotection in multiple experimental models. Thus, in addition to symptomatic benefits, rasagiline offers the promise of clinically relevant neuroprotection.

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

“…MAO, which is classified as type A or B, breaks down biogenic amines, including neurotransmitters [4,5]. Both MAO isoenzymes degrade dopamine, but display different specificities for other neurotransmitters and amines [4].…”

Treatment of Motor Symptoms in Idiopathic Parkinson’s Disease

“…Monoamine oxidase type B inhibitors Selegiline and rasagiline reduces the destruction of dopamine by inhibiting the monoamine oxidase type B (MAO-B) isoenzyme (6). Although there are studies reporting the disease-modifying effect of rasagiline, this effect has not been supported in subsequent studies (7,8).…”

Role of rasagiline in treating Parkinson’s disease: effect on disease progression

“…It also has a role in deaminating betaphenylethylamine, which stimulates release of dopamine and inhibits its reuptake. 5 Therefore, inhibition of MAO-B increases available dopamine.…”

“…Rather, rasagiline is a secondary cyclic benzylamine and indane derivative 5 with the chemical structure (n-propargyl-1[r]-aminoindan). It is rapidly absorbed and undergoes metabolism by the cytochrome P450 (CYP) hepatic enzymes, primarily CYP1A2.…”

“…It is rapidly absorbed and undergoes metabolism by the cytochrome P450 (CYP) hepatic enzymes, primarily CYP1A2. 5 Therefore, it should be avoided in patients with moderate to severe hepatic insufficiency. …”