Four major components of the mechanism of action have been identified for t
he antiparkinsonian drug budipine up to now. 1) The primary action of budip
ine 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), whi
ch in sum might be responsible for enhancing the endogenous dopaminergic ac
tivity. 2) Radioligand and functional studies at the N-methyl-D-aspartate (
NMDA) type glutamate receptor characterize budipine as a low-affinity, unco
mpetitive antagonist with fast kinetics and moderate voltage-dependency at
the phencyclidine (PCP) binding site, comparable to that observed with aman
tadine, thereby counteracting an increased excitatory glutamatergic activit
y. 3) The antimuscarinic action of budipine, verified by functional and bin
ding studies at native muscarinic M-1-M-3 and human recombinant m1-m5 recep
tor subtypes in vitro, is up to 125-fold weaker than that of biperiden and
corresponds to its approximately 100-fold lower potency to cause experiment
ally-induced peripheral antimuscarinic effects and explains only part of it
s high potency, which equals biperiden, to suppress cholinergically evoked
tremor. 4) An additional inhibition of striatal gamma-aminobutyric acid (GA
BA) release by budipine may be beneficial to suppress an increased striatal
GABAergic output activity. The contribution of other observed effects to t
he therapeutic action of budipine, i.e. weak stimulation of noradrenaline a
nd serotonin release, binding to brain sigma, receptors and blockade of his
tamine H-1 receptors, is not yet clear. By means of these multiple mechanis
ms, budipine might correct the imbalance of striatal output pathways by res
toring DA levels in the striatum, and positively influence the secondary ch
anges in other transmitter systems (glutamate, acetylcholine, GABA) observe
d in Parkinson's disease.