Budipine, a NMDA receptor antagonist, as a low-affinity, uncompetitive antagonist with fast kinetics and moderate voltage-dependency at the phencyclidine (PCP) binding site, comparable to that observed with amantadine, thereby counteracting an increased excitatory glutamatergic activity. The primary action of budipine is an indirect dopaminergic effect as shown by facilitation of dopamine (DA) release, inhibition of monoamine oxidase type B (MAO-B) and of DA (re) up-take and stimulation of aromatic L-amino acid decarboxylase (AADC), which in sum might be responsible for enhancing the endogenous dopaminergic activity. An additional inhibition of striatal gamma-aminobutyric acid (GABA) release by budipine may be beneficial to suppress an increased striatal GABAergic output activity[3]. In striatal neurones, budipine blocked outward currents at +70 mV with an IC50 of 827 microM, suggesting that the binding site is less deep in the channel (delta = 0.45) than for memantine. Budipine exhibited concentration-dependent open channel blocking kinetics (kappa(on) = 0.71 x 10(4) M(-1) s(-1)) whereas the fast offset rate was concentration-independent (kappa(off) = 0.63 s(-1)). Calculation of the ratio kappa(off)/kappa(on) revealed an apparent Kd value of 88.7 microM[4]. NMDA antagonistic action of budipine is at least partly responsible for its antiparkinsonian activity[5]. 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[6]. Budipine and TPM (topiramate) are an effective drug combination in stopping self-sustained status epilepticus, and TPM alone was neuroprotective, despite the continuation of seizure activity[7].
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