(−)-1-(Benzofuran-2-yl)-2-propylaminopentane enhances locomotor activity in rats due to its ability to induce dopamine release

Abstract

“Catecholaminergic and serotoninergic activity enhancer” effects are newly found mechanisms of action of a class of compound that enhance impulse propagation-mediated release of catecholamines and serotonin in the brain. In the present study, (−)-1-(benzofuran-2-yl)-2-propylaminopentane hydrochloride [(−)-BPAP HCl], a compound with selective and potent “catecholaminergic and serotoninergic activity enhancer” effects, was tested for its efficacy to potentiate locomotor activity in normal rats and to attenuate hypolocomotion in reserpine-treated rats. (−)-BPAP HCl potentiated locomotor activity in non-habituated rats during a 2-h observation period dose-dependently (0.3–10 mg/kg). (−)-BPAP HCl (1–3 mg/kg) was also effective to reverse reserpine-induced hypolocomotion. The effects of (−)-BPAP HCl in normal and reserpine-treated rats were attenuated by the dopamine D1 receptor antagonist, R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1 H-3-benzazepine (SCH 23390), suggesting that the effects of (−)-BPAP HCl were mediated by activation of the dopaminergic system. In addition, the administration of (−)-BPAP HCl increased ipsilateral turning in unilaterally 6-hydroxydopamine-lesioned rats, implying presynaptic activation of nigrostriatal dopaminergic terminals by (−)-BPAP HCl. Furthermore, although antiparkinsonian agents, such as apomorphine and amantadine, failed to improve reserpine-induced ptosis, (−)-BPAP HCl significantly improved ptosis. These findings suggested that a “catecholaminergic and serotoninergic activity enhancer” compound, (−)-BPAP, stimulates motor function in rats and improves motor deficits in animal models of Parkinson's disease due to its ability to induce dopamine release.