Evolution of anti-parkinsonian activity of monoterpenoid (1R,2R,6S)-3-methyl-6-(prop-1-en-2-yl)cyclohex-3-ene-1,2-diol in various in vivo models

Abstract

It has been found recently that monoterpenoid (1R,2R,6S)-3-methyl-6-(prop-1-en-2-yl)cyclohex-3-ene-1,2-diol (Diol) demonstrates high antiparkinsonian activity in some animal models. We carried out an extended study of the antiparkinsonian activity of Diol in a set of relevant animal models. Diol (20mg/kg) exhibited an anticataleptogenic effect in the haloperidol-induced catalepsy model and restored motor activity in animals in the reserpine-induced model of oligokinesia. The ability of Diol singly administered before MPTP injection to reduce rigidity comparable to that of activity of L-DOPA (100mg/kg) was found using the model of Parkinsonian syndrome (PS) induced by single injection of MPTP (30mg/kg) to C57BL/6 mice. In the model of PS induced by subchronic administration of MPTP (4 × 20mg/kg), Diol at a dose of 20mg/kg reduced rigidity with effectiveness comparable to that of L-DOPA, while being superior to L-DOPA in terms of its effect on motor activity. It was found using the model of PS induced by systemic administration of rotenone that subchronic daily oral administration of Diol prior to rotenone injection reduced severity of PS in rats. Assessment of the effects of chronic administration of Diol (20mg/kg) and L-DOPA to animals with 6-OHDA-induced PS showed that administration of Diol alleviated the symptoms of sensorimotor deficit in right limbs in rats. Thus, the potent antiparkinsonian activity of Diol was demonstrated in all the used rodent models experiments. Diol (20mg/kg) is as effective as the comparator agent L-DOPA administered at doses of 50–100mg/kg.