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

Seiichiro Shimazu, Kazue Takahata, Hiroshi Katsuki, Hiroko Tsunekawa, Akie Tanigawa, Fumio Yoneda, Joseph Knoll, Akinori Akaike

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25 Citations (Scopus)

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-1H-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.

Original languageEnglish
Pages (from-to)181-189
Number of pages9
JournalEuropean Journal of Pharmacology
Volume421
Issue number3
DOIs
Publication statusPublished - Jun 15 2001

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Keywords

  • ( - )-Deprenyl
  • 6-Hydroxydopamine
  • Catecholaminergic and serotoninergic activity enhancer
  • Parkinson's disease
  • Reserpine
  • [( - )-BPAP HCl] ( - )-1-(benzofuran-2-yl)-2-propylaminopentane hydrochloride

ASJC Scopus subject areas

  • Pharmacology

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