Synthesis and monoamine oxidase inhibitory activities of .alpha.-allenic amines in vivo and in vitro. Different activities of two enantiomeric allenes

Abstract

A series of 15 .alpha.-allenic amines, including primary, secondary and tertiary ones [including 2-(4-chlorobenzyl)-2,3-butadienylaminium hydrogen oxalate, 2-(4-methylbenzyl)-2,3-butadienylaminium hydrogen oxalate, 2-(4-methoxybenzyl)-2,3-butadienylaminium hydrogen oxalate, N-2,3-butadienylbenzylamine, N-2,3-butadienyl-.alpha.,N-dimethylphenethylamine, N-2,3-butadienyl-N-methyl-2-(2,4-dichlorophenoxy)propylamine, N-2,3-butadienyl-N-methyl-1-indanamine and 2-(2,3-butadienyl)-1,2,3,4-tetrahydroisoquinoline], was synthesized, partly by organocopper chemistry. Their ability to inhibit mouse and rat brain mitochondrial monoamine oxidase (MAO) in vivo and in vitro, respectively, was evaluated. Almost all compounds were quite potent inhibitors of MAO, some as potent as deprenyl. Like deprenyl, most of the compounds were selective inhibitors of the B form of MAO. The 2 enantiomeric forms of N-methyl-N-(2,3-pentadienyl)benzylamine (2) were prepared and the R-(-)-form was 2.7 times as active as the (+) form in vivo and 25 times as active in vitro. Most of the compounds were tested for their ability to potentiate the phenylethylamine (PEA) response in mice, and a good correlation between the potency of MAO inhibition and PEA potentiation was found. The only compound tested did not potentiate the blood pressure response to tyramine.