Budipine Hydrochloride

Publisher Summary This chapter focuses on antiglutamatergic drugs in the treatment of Parkinson's disease (PD). In the vertebrate brain, glutamate is the main excitatory neurotransmitter and mediates neurotransmission of most excitatory synapses. Glutamate-mediated synaptic transmission is essential for the normal functioning of the central nervous system. The ideal antiglutamatergic drug should largely be able to block the N-methyl-D-aspartate (NMDA) receptor in situations of excessive activation but without altering glutamatergic transmission during normal conditions. Amantadine is the only antiglutamatergic agent used in the management of PD patients and is particularly useful for the treatment of levodopa-induced dykinesias. Amantadine interacts with several different neurotransmitters systems and exhibits dopaminergic and anticholinergic properties along with antagonist activity of NMDA glutamatergic receptors. Amantadine exhibits mild antiparkinsonian effect and is more effective in the control of bradykinesia and rigidity than in tremor. It also exhibits neuroprotective properties in addition to its symptomatic effects. The chapter also describes some other antiglutamatergic drugs, namely memantine, dextromethorphan, budipine, and riluzole.

NMDA receptors play a role in the aetiology of depression with non-competitive NMDA receptor antagonists such as amantadine showing synergy with conventional antidepressants. To advance a neurochemical rational for these findings, we have studied the effects of administration of amantadine and budipine with the antidepressants reboxetine (REB), paroxetine (PAROX) and clomipramine (CLOM) on extracellular DA in rats using microdialysis. Acutely, amantadine (40 mg/kg) or budipine (10 mg/kg) did not significantly alter extracellular DA. REB (10 mg/kg), PAROX (10 mg/kg) both increased cortical DA while CLOM (10 mg/kg) produced a decrease. When amantadine or budipine was administered 30 min before the antidepressants, DA increases were markedly greater than following the antidepressants alone. Chronically drug effects were studied at 4, 7, 14 and 21 days. Amantadine and budipine did not significantly alter extracellular DA at any time. The three antidepressants elicited a gradual increase in DA which became significant after 7 days and tended to plateau thereafter. When amantadine (20 mg/kg) or budipine (5 mg/kg) was co-administered with the three antidepressants, two differences were seen compared with the antidepressants alone. Firstly, the time required for significant increases in cortical DA was reduced with elevated levels now being observed by 4 days. Secondly, the increase in extracellular DA was greater in these rats throughout the experiment. If increased extracellular DA represents a step in the mechanism of action of antidepressants, these data suggest that combined treatment with clinically tolerated NMDA antagonists such as amantadine could reduce the delay in therapeutic onset of antidepressants and possibly enhance their efficacy.