Effect of 1-aminoadamantanes on the MAO activity in brain, liver, and kidney of the rat.

In order to elucidate the possible interference of the antiparkinson drug 1-aminoadamantane (D-1, PK Merz) and the antispastic compound 1,3-dimethyl-5-aminoadamantane (DMAA, D-145, memantine, Memantine) on neurotransmitter metabolism, the effect of D-1 and its C-alkyl derivatives memantine, 1-amino-3,5,7-trimethyladamantane (D-191), and 1-amino-3-(n)-butyladamantane (D-178) on MAO activity in brain, liver, and kidney of the rat was investigated. A radioisotope method using [14C]5-hydroxytryptamine as substrate was used. The highest MAO activity was found in liver followed by brain and kidney (Vmax: 137, 64, and 26 nmol/mg protein X h, respectively). The Km values did not differ significantly for the three tissues (liver: 107 mumol/l; brain: 96 mumol/l; kidney: 86 mumol/l). The MAO activity in liver, brain and kidney was noncompetitively inhibited by all 1-aminoadamantanes studied, each derivative, respectively, showing in all three tissues about the same percentage inhibition. The inhibitory activity was found to be increased with the degree of C-alkylation: D-1 (Ki approximately 1 mmol/l) less than D-145 (Ki approximately 0.1 mmol/l) less than D-191 (Ki approximately 0.07 mmol/l) less than D 178 (Ki approximately 0.02 mmol/l).

Citation

W Wesemann, O Ekenna. Effect of 1-aminoadamantanes on the MAO activity in brain, liver, and kidney of the rat. Arzneimittel-Forschung. 1982;32(10):1241-3

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PMID: 6891223

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