(-)-1-(Benzofuran-2-yl)-2-propylaminopentane enhances locomotor activity in rats due to its ability to induce dopamine release.
"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.
Shimazu
S
S
Institute of Research and Development, Fujimoto Pharmaceutical Corporation, 1-3-40 Nishiotsuka, Osaka 580-8503, Matsubara, Japan.
Takahata
K
K
Katsuki
H
H
Tsunekawa
H
H
Tanigawa
A
A
Yoneda
F
F
Knoll
J
J
Akaike
A
A
D000547:Amantadine / Q000494:pharmacology; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D001572:Benzofurans / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006185:Habituation, Psychophysiologic; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D016627:Oxidopamine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012110:Reserpine / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism
C404200:1-(benzofuran-2-yl)-2-propylaminopentane; D014150:Antipsychotic Agents; D001552:Benzazepines; D001572:Benzofurans; D015259:Dopamine Agents; D018492:Dopamine Antagonists; D012110:Reserpine; D016627:Oxidopamine; D000547:Amantadine; D004298:Dopamine