ANTIPARKINSONIAN AND OTHER MOTOR EFFECTS OF FLUPIRTINE ALONE AND IN COMBINATION WITH DOPAMINERGIC DRUGS

In this study we attempted to specify the behavioural profile of the a nalgesic flupirtine (1, 10 and 20 mg/kg p.o.) in the rat with respect to (i) its antiparkinsonian potential alone and as an adjunct to L-dih ydroxyphenylalanine (L-DOPA) in the haloperidol-induced catalepsy (0.5 mg/kg haloperidol i.p.), (ii) locomotion and exploratory behaviour in the open field with holeboard, and (iii) possible psychomotor stimula ting effects in the experimental chamber. In the two latter tests, beh aviour was additionally challenged by D-amphetamine (2 mg/kg i.p.). In the catalepsy tests (horizontal bar, podium, grid) flupirtine alone w as anticataleptic at doses of 10 and 20 mg/kg p.o., and the antiparkin sonian potential of a subthreshold dose of L-DOPA (50 mg/kg p.o.) was potentiated by 1 and 10 mg/kg p.o. flupirtine. On spontaneous forward locomotion in the open field with holeboard flupirtine (1 and 10 mg/kg p.o.) had no marked effect but increased the frequency and duration o f head dips, indicative for augmenting exploratory behaviour. Spontane ous rearing was reduced and D-amphetamine-induced rearing was enhanced by 1 mg/kg p.o. flupirtine. Grooming was reduced by 1 and 10 mg/kg p. o. flupirtine. In contrast, turning and grooming behaviour (spontaneou s as well as D-amphetamine-induced) was not markedly influenced by flu pirtine in the experimental chamber. Sniffing was increased in this te st by 1 mg/kg p.o. flupirtine but not by the higher dose. Flupirtine i s highly effective in antagonising neuroleptic-induced catalepsy as we ll as in potentiating L-DOPA treatment in the rat, suggesting it is a prospective new candidate for the therapy of Parkinson's disease.