Aza analogues of amantadine - efficient neurotransmitter modulators for in vivo models
M. P. PITUKHIN1, I. V. SOROKINA1, S. V. AYDAGULOVA1,2, K. YU. PONOMAREV1, YU. V. MESHKOVA1, T. G. TOLSTIKOVA1, E. V. SUSLOV1, K. P. VOLCHO1
1Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia
2Novosibirsk State Medical University, Novosibirsk, Russia
Keywords: amantadine, azaadamantanes, dopaminergic, cholinergic, adrenergic modulators
Abstract
Neuromodulatory properties of two aza analogues of amantadine - 6-amino-5,7-dimethyl-1,3 -diazaadamantane 3 and 7-amino-1,3,5-triazaadamantane 4, as well as a synthetic precursor of compound 3 - 5,7-dimethyl-1,3-diazaadamantan-6-one 2, - were investigated in experiments on outbred male mice. Azaadamantanes and the reference drug amantadine hydrochloride 1 were administered intraperitoneally in an aqueous solution at a dose of 20 mg/kg. Control animals were administered water. In a model of neuroleptic haloperidol-induced parkinsonism, it has been shown that 2 and 4 are more potent agents in dopamine-stimulating activity than amantadine. In the model of arecoline tremor, azaadamontanes 3 and 4 were found to have higher M-cholinergic blocking activity than amantadine. All azaadamantanes have been shown to potentiate adrenergic neurotransmission but do not have GABAergic activity. The most promising agent is triazaadamantane 4, which has demonstrated pronounced dopamine-stimulating and M-cholinergic blocking properties with moderate adrenergic activity.
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