Why drugs like budipine which work mainly on non dopamine route are forgotten even though there are so much research proving its effectiveness and safety?
I site below only 2 out of many other papers.
Imad


J Neural Transm Suppl. 1999;56:83-105.

Multiple mechanisms of action: the pharmacological profile of budipine.
Eltze M.

Abstract
Four major components of the mechanism of action have been identified for the antiparkinsonian drug budipine up to now. 1) 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. 2) Radioligand and functional studies at the N-methyl-D-aspartate (NMDA) type glutamate receptor characterize budipine 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. 3) The antimuscarinic action of budipine, verified by functional and binding studies at native muscarinic M1-M3 and human recombinant m1-m5 receptor subtypes in vitro, is up to 125-fold weaker than that of biperiden and corresponds to its approximately 100-fold lower potency to cause experimentally-induced peripheral antimuscarinic effects and explains only part of its high potency, which equals biperiden, to suppress cholinergically evoked tremor. 4) An additional inhibition of striatal gamma-aminobutyric acid (GABA) release by budipine may be beneficial to suppress an increased striatal GABAergic output activity. The contribution of other observed effects to the therapeutic action of budipine, i.e. weak stimulation of noradrenaline and serotonin release, binding to brain sigma1 receptors and blockade of histamine H1 receptors, is not yet clear. By means of these multiple mechanisms, budipine might correct the imbalance of striatal output pathways by restoring DA levels in the striatum, and positively influence the secondary changes in other transmitter systems (glutamate, acetylcholine, GABA) observed in Parkinson's disease.

PMID: 10370904 [PubMed - indexed for MEDLINE]
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Budipine in Parkinson's tremor
Heinz Reichmann
Abstract
It is generally accepted that patients with a tremor-dominant type of idiopathic Parkinson's disease progress more slowly than the ones with the rigid-akinetic type. On the other hand successful treatment of Parkinsonian tremor is a challenge. German neurologists use anticholinergics, budipine, β-blockers, clozapine, dopaminergic substances and for most severe cases deep brain stimulation. Budipine is an enigma because its main mode of action is still unknown, although it is mostly listed under glutamate antagonists. There is however no other anti-Parkinsonian drug available with such a broad spectrum of action as shown for budipine. Budipine has been studied in open and double-blind studies as monotherapy and adjunct therapy. In both instances the drug showed beneficial effects to the patients. It may well be that the non-dopaminergic mode of action of budipine is helpful even for patients who are on stable medication. When 3 years ago reports on budipine-induced prolongation of the QT interval in the ECG emerged larger trials were stopped and nowadays there are strict rules on how to use budipine. Nonetheless, budipine in our hands is a most useful and safe drug to treat tremor and other main symptoms of Parkinson's disease.
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