Effect of coadministration of glutamate receptor antagonists and dopaminergic agonists on locomotion in monoamine-depleted rats.
Combinations of dopaminergic agonists with glutamate receptor antagonists have been suggested to be a possible alternative treatment of Parkinson's disease. To gain further insights into this possibility, the antagonist of the competitive AMPA-type glutamate receptor NBQX and the ion-channel blocker of the NMDA glutamate receptor (+)-MK-801 in combination with the dopamine D1 receptor agonists: SKF 38393, SKF 82958 and dihydrexidine; the dopamine D2 receptor agonist bromocriptine and the dopamine-precursor L-DOPA were tested in rats pretreated with reserpine and alpha-methyl-p-tyrosine. MK-801 on its own induced locomotor behaviour and potentiated the antiakinetic effects of dihydrexidine and L-DOPA but not of the other dopamine agonists tested. NBQX neither on its own nor coadministered with the dopamine agonists tested had an antiakinetic effect. These results indicate that agents, blocking the ion-channel of the NMDA receptor, might be useful adjuvants to some but not all dopaminomimetics in therapy of Parkinson's disease. The same does not seem to be true for the AMPA-antagonist NBQX.
Gossel
M
M
Department of Pharmacology, Merz + Co., Frankfurt/Main, Federal Republic of Germany.
Schmidt
W J
WJ
Löscher
W
W
Zajaczkowski
W
W
Danysz
W
W
D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism*; D001971:Bromocriptine / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology*; D004338:Drug Combinations; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000819:agonists
D015306:Biogenic Monoamines; D018491:Dopamine Agonists; D004338:Drug Combinations; D018691:Excitatory Amino Acid Antagonists; D011810:Quinoxalines; D017447:Receptors, Dopamine D1; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D001971:Bromocriptine; D016291:Dizocilpine Maleate