title: Structure-activity studies leading to (-)1-(benzofuran-2-yl)-2-propylaminopentane, ((-)BPAP), a highly potent, selective enhancer of the impulse propagation mediated release of catecholamines and serotonin in the brain.
abstract: The catecholaminergic and serotoninergic neurons in the brain change their performance according to the physiological need via a catecholaminergic/serotoninergic activity enhancer (CAE/SAE) mechanism. Phenylethylamine (PEA), tyramine and tryptamine are the presently known endogenous CAE/SAE substances which enhance the impulse propagation mediated release of catecholamines and serotonin in the brain. A PEA derivative, (-)deprenyl (selegiline), known as a selective inhibitor of MAO-B, is for the time being the only CAE/SAE substance in clinical use. Aiming to develop a selective CAE/SAE substance much more potent than (-)deprenyl, a series of new 1-aryl-2-alkylaminoalkanes, structurally unrelated to PEA and the amphetamines, was designed and prepared. Among them, (-)1-(benzofuran-2-yl)-2-propylaminopentane ((-)BPAP) was selected as a promising candidate substance for further studies. (-)BPAP significantly enhanced in rats the impulse propagation mediated release of catecholamines and serotonin in the brain 30min after acute injection of 0.36nmol/kg sc. In the shuttle box, (-)BPAP was in rats about 130 times more potent than (-)deprenyl in antagonizing tetrabenazine induced inhibition of performance. (+/-)BPAP protected cultured hippocampal neurons from the neurotoxic effect of beta-amyloid in 10(-14)-10(-15)M concentration.
authors.affiliation: Research Institute, Fujimoto Pharmaceutical Corporation, Matsubara, Osaka 580-8503, Japan. soyaku@fujimoto-pharm.co.jp
authors.forename: F
authors.initials: F
authors.lastname: Yoneda
authors.forename: T
authors.initials: T
authors.lastname: Moto
authors.forename: M
authors.initials: M
authors.lastname: Sakae
authors.forename: H
authors.initials: H
authors.lastname: Ohde
authors.forename: B
authors.initials: B
authors.lastname: Knoll
authors.forename: I
authors.initials: I
authors.lastname: Miklya
authors.forename: J
authors.initials: J
authors.lastname: Knoll
mesh_terms: D000662:Amphetamines / Q000138:chemical synthesis / Q000494:pharmacology; D000682:Amyloid / Q000032:analysis / Q000037:antagonists & inhibitors; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001572:Benzofurans / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000502:physiology; D001933:Brain Stem / Q000378:metabolism; D002395:Catecholamines / Q000378:metabolism*; D002478:Cells, Cultured; D004558:Electric Stimulation; D006624:Hippocampus / Q000166:cytology; D008995:Monoamine Oxidase / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D010627:Phenethylamines / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D012642:Selegiline / Q000737:chemistry / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014363:Tryptamines / Q000494:pharmacology; D014439:Tyramine / Q000494:pharmacology
chemical_list: C404200:1-(benzofuran-2-yl)-2-propylaminopentane; D000662:Amphetamines; D000682:Amyloid; D001572:Benzofurans; D002395:Catecholamines; D010627:Phenethylamines; D014363:Tryptamines; D012642:Selegiline; D012701:Serotonin; C030820:tryptamine; D008995:Monoamine Oxidase; D014439:Tyramine