Budipine is a novel antiparkinsonian
drug which is particularly beneficial in the treatment of parkinsonian
tremor. The mechanism of action of
budipine is not fully understood. To study whether
budipine has dopaminergic activity in vivo, we used the
6-hydroxydopamine rotational model of
Parkinson's disease.
Budipine (0.78-12.5 mg/kg i.p.) did not induce ipsilateral or contralateral rotations, suggesting that it does not possess direct or indirect dopaminergic activity. This conclusion is further supported by the observation that
budipine (10 mg/kg) i.v. did not facilitate striatal
dopamine release measured in vivo by brain microdialysis. To investigatate possible
antimuscarinic and
N-methyl-D-aspartic acid (
NMDA) antagonistic properties of
budipine, we compared
budipine with the
antimuscarinic antiparkinsonian
drug biperiden and the
NMDA receptor antagonist 3-[(+/-)-2-carboxypiperazine-4-yl]-propyl-1-
phosphonic acid (
CPP). In receptor-binding assays,
budipine inhibited thienylcyclohexylpiperidyl-3,4-[3H](n) ([I3H]TCP) (2.5 nM)-binding with an IC50 of 36 microM and [3H]3-quinuclidinol benzilate-binding with an IC50 of 1.1 microM. The respective values for
biperiden were 170 and 0.053 microM. In line with these findings,
budipine and
CPP increased the threshold for
NMDA-induced
seizures in mice with an ED50 of 10.2 and 4.4 mg/kg, respectively, whereas
biperiden was not effective. In 6-hydroxydopamine-lesioned rats,
budipine (3.13-12.5 mg/kg) and
CPP (0.1-0.39 mg/kg) increased the number of contralateral rotations induced by
apomorphine, whereas
biperiden was not effective. The present data suggest that
budipine acts by blocking
muscarinic and
NMDA transmission while facilitation of dopaminergic transmission does not appear to contribute to its in vivo action. In comparison to
biperiden, which has also
antimuscarinic and
NMDA receptor antagonistic properties, the anti-
NMDA action of
budipine is more prominent.