Motor actions of eliprodil in the normal and monoamine-depleted mouse: a role in the treatment of Parkinson's disease?
The non-competitive NMDA polyamine site antagonist, eliprodil, was examined for its effects on exploratory activity in non-habituated mice and for its antiakinetic potential in reserpine-treated mice. A low dose of eliprodil (5 mg/kg) weakly stimulated locomotion in naive animals, whilst higher doses depressed rearing (20-40 mg/kg) and grooming (40 mg/kg), consistent with a sedative action. At no dose did eliprodil cause ataxia. In 24 h reserpine-treated mice, eliprodil (10-40 mg/kg) reversed akinesia, but this effect was subject to considerable inter-animal variation and was not statistically significant. Eliprodil did not alter the motor recovery elicited by the dopamine D1 agonist SKF 38393, or the dopamine D2 agonist RU 24213, and suppressed the motor stimulation induced by L-DOPA. These results indicate that eliprodil displays a far lower propensity than many other NMDA receptor antagonists for disturbing posture and gait, but lacks the essential motor stimulant action required to make it a safe and effective antiparkinsonian agent, at least in the reserpine-treated mouse model of Parkinson's disease.
Brooks
S
S
Psychology Division, University of Hertfordshire, Hatfield, United Kingdom.
Kaur
S
S
Starr
B S
BS
Starr
M S
MS
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D015306:Biogenic Monoamines / Q000378:metabolism*; D004195:Disease Models, Animal; D015259:Dopamine Agents / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004525:Efferent Pathways / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D007980:Levodopa / Q000494:pharmacology; D008124:Locomotion / Q000187:drug effects; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009046:Motor Neurons / Q000187:drug effects* / Q000502:physiology; D010300:Parkinson Disease / Q000188:drug therapy*; D010627:Phenethylamines / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology*; D017447:Receptors, Dopamine D1 / Q000819:agonists; D012110:Reserpine / Q000494:pharmacology; D013565:Sympatholytics / Q000494:pharmacology
D015306:Biogenic Monoamines; D015259:Dopamine Agents; D018491:Dopamine Agonists; D018691:Excitatory Amino Acid Antagonists; D010627:Phenethylamines; D010880:Piperidines; D017447:Receptors, Dopamine D1; D013565:Sympatholytics; D007980:Levodopa; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; C016868:N-n-propyl-N-phenylethyl-4(3-hydroxyphenyl)ethylamine hydrochloride; D012110:Reserpine; C058083:eliprodil