1-(Benzofuran-2-yl)-2-(3,3,3-trifluoropropyl)aminopentane HCl, 3-F-BPAP, antagonizes the enhancer effect of (-)-BPAP in the shuttle box and leaves the effect of (-)-deprenyl unchanged.
The subcutaneous administration of 1 mg/kg tetrabenazine, once daily for 5 days, which depletes the catecholamine stores in the brain, significantly inhibits in rats the acquisition of a two-way conditioned avoidance reflex in the shuttle box. Enhancer substances, the tryptamine-derived selective and highly potent enhancer, R-(-)-1-(benzofuran-2-yl)-2-propylaminopentane HCl [(-)-BPAP] (0.05-10 mg/kg), the beta-phenylethylamine (PEA)-derived enhancer, (-)-deprenyl (1-5 mg/kg) and the (-)-deprenyl analogue, free of MAO-B inhibitory potency, (-)-1-phenyl-2-propylaminopentane HCl [(-)-PPAP], (1-5 mg/kg), antagonize in a dose-dependent manner the inhibition of learning caused by tetrabenazine. 1-(Benzofuran 2 yl)-2-(3,3,3-trifluoropropyl)aminopentane HCl [3 F BPAP], a newly synthetized analogue of (-)-BPAP with low specific activity, significantly antagonized the enhancer effect of (-)-BPAP but left the effect of (-)-deprenyl and (-)-PPAP unchanged. This is the first proof for a difference in the mechanism of action between a PEA-derived enhancer substance and its tryptamine-derived peer.
Knoll
Joseph
J
Department of Pharmacology and Pharmacotherapy, Faculty of General Medicine, Semmelweis University, P.O.B. 370, H-1445 Budapest, Hungary. jozsefknoll@hotmail.com
Miklya
Ildikó
I
Knoll
Berta
B
Yasusa
Takuya
T
Shimazu
Seiichiro
S
Yoneda
Fumio
F
D018759:Adrenergic Uptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D001362:Avoidance Learning / Q000187:drug effects*; D001572:Benzofurans / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D066298:In Vitro Techniques; D007279:Injections, Subcutaneous; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D012642:Selegiline / Q000494:pharmacology*; D012701:Serotonin / Q000378:metabolism; D013747:Tetrabenazine / Q000008:administration & dosage / Q000494:pharmacology
C404200:1-(benzofuran-2-yl)-2-propylaminopentane; D018759:Adrenergic Uptake Inhibitors; D000978:Antiparkinson Agents; D001572:Benzofurans; D012642:Selegiline; D012701:Serotonin; D004298:Dopamine; D009638:Norepinephrine; D013747:Tetrabenazine