Longevity study with low doses of selegiline/(-)-deprenyl and (2R)-1-(1-benzofuran-2-yl)-N-propylpentane-2-amine (BPAP)

Abstract

AIMS: The first longevity study demonstrating that rats treated with the MAO-B inhibitory dose of (-)-deprenyl (0.25mg/kg) lived significantly longer than their saline-treated peers was published in 1988, and corroborated in many papers. The recent findings that (-)-deprenyl is primarily a PEA-derived synthetic catecholaminergic activity enhancersubstance; (2R)-1-(1-benzofuran-2-yl)-N-propylpentane-2-amine (BPAP) is a tryptamine-derived synthetic enhancer substance, initiated our first longevity study on rats with low enhancer doses of (-)-deprenyl and BPAP to test the enhancer effect's role inlife extension. MAIN METHODS: We used the shuttle box technique for selecting the optimum doses of (-)-deprenyl and BPAP. (-)-Deprenyl exerts in rats in 0.001mg/kg its 'specific' enhancer effect and in 0.1mg/kg its 'non-specific' enhancer effect. BPAP exerts its 'specific' enhancer effect in 0.0001mg/kg and its 'non-specific' enhancer effect in 0.05mg/kg. Groups of male Wistar rats (N=40) were treated subcutaneously from their 10th week until death, three times weekly, with saline (0.5ml/kg), and the selected doses of (-)-deprenyl or BPAP, respectively. As an indicator of aging we tested the age-related changes in their learning ability. KEY FINDINGS: Rats treated with 0.0001 or 0.05mg/kg BPAP lived significantly longer than their saline treated peers (P<0.02) and BPAP was more potent in extending rats' lifespan than (-)-deprenyl. 18-month-old rats treated with 0.0001mg/kg BPAP were as good learners as 3-month-old saline treated rats. SIGNIFICANCE: The study revealed that the enhancer effect is responsible for life extension.