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N-methyl-D-aspartate receptor antagonist and dopamine D1 and D2 agonist interactions in 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine-induced hemiparkinsonian monkeys. 1993

E F Domino, and J Sheng
Department of Pharmacology, University of Michigan, Ann Arbor.

The noncompetitive N-methyl-D-aspartate antagonist (5R,10S)-(+)-5-methyl- 10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate (MK-801) and three dopamine agonists [(+/-)6-chloro-7,8-dihydroxy-2,3,4,5-tetrahydro-1-phenyl-1H-3-benzazepin e hydrobromide (SKF-81297), (+/-)6,chloro-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5- tetrahydro-1H-3-benzazepine hydrobromide (SKF-82958) selective for D1 and (-)-2-[N-propyl-N-(2-thienyl)ethyl-amino-5- hydroxytetralin] hydrochloride (N-0923) selective for D2 receptors] were studied in seven adult female hemiparkinsonian Macaca nemestrina monkeys. Video recordings of free circling behavior showed that both SKF-82958 and N-0923 produced dose-related mean increases in contraversive rotations during the 120-min period after i.m. injection. SKF-81297 (21.1, 67.8 and 210.7 micrograms/kg) was relatively inactive compared to SKF-82958 (24.8, 74.8 and 234 micrograms/kg). The selective D2 agonist N-0923 (3.2, 10 and 32 micrograms/kg, i.m.) was the most potent in producing contraversive circling behavior. The noncompetitive N-methyl-D-aspartate antagonist dizocilpine (MK-801), in doses of 10 and 32 micrograms/kg i.m., produced a very slight increase in contraversive circling in contrast to the selective dopamine agonist SKF-82958. A large dose (100 micrograms/kg, i.m.) of MK-801 produced marked central nervous system depression. In combination with the dopamine agonists N-0923 and SKF-82958, MK-801 depressed contraversive circling in all doses studied. This study using hemiparkinsonian monkeys does not support the suggestion that a noncompetitive N-methyl-D-aspartate antagonist such as MK-801 would be useful in adjunctive therapy of human Parkinson's disease.

UI MeSH Term Description Entries
D008124 Locomotion Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. Locomotor Activity,Activities, Locomotor,Activity, Locomotor,Locomotor Activities
D008254 Macaca nemestrina A species of the genus MACACA which inhabits Malaya, Sumatra, and Borneo. It is one of the most arboreal species of Macaca. The tail is short and untwisted. M. leonina,Macaca nemestrina leonina,Macaca nemestrina pagensis,Macaca nemestrina siberu,Macaca siberu,Monkey, Pig-Tailed,Pagai Macaque,Pig-Tail Macaque,Pig-Tailed Macaque,Pig-Tailed Monkey,M. pagensis,Macaca pagensis,Monkey, Pigtail,Monkey, Pigtailed,Pigtail Macaque,Macaque, Pagai,Macaque, Pig-Tail,Macaque, Pig-Tailed,Macaque, Pigtail,Monkey, Pig Tailed,Pagai Macaques,Pig Tail Macaque,Pig Tailed Macaque,Pig Tailed Monkey,Pig-Tail Macaques,Pig-Tailed Macaques,Pig-Tailed Monkeys,Pigtail Macaques,Pigtail Monkey,Pigtail Monkeys,Pigtailed Monkey,Pigtailed Monkeys
D009043 Motor Activity Body movements of a human or an animal as a behavioral phenomenon. Activities, Motor,Activity, Motor,Motor Activities
D010302 Parkinson Disease, Secondary Conditions which feature clinical manifestations resembling primary Parkinson disease that are caused by a known or suspected condition. Examples include parkinsonism caused by vascular injury, drugs, trauma, toxin exposure, neoplasms, infections and degenerative or hereditary conditions. Clinical features may include bradykinesia, rigidity, parkinsonian gait, and masked facies. In general, tremor is less prominent in secondary parkinsonism than in the primary form. (From Joynt, Clinical Neurology, 1998, Ch38, pp39-42) Atherosclerotic Parkinsonism,Secondary Parkinsonism,Symptomatic Parkinson Disease,Parkinson Disease, Secondary Vascular,Parkinson Disease, Symptomatic,Parkinsonism, Secondary,Parkinsonism, Symptomatic,Secondary Vascular Parkinson Disease,Parkinsonism, Atherosclerotic,Secondary Parkinson Disease,Symptomatic Parkinsonism
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004347 Drug Interactions The action of a drug that may affect the activity, metabolism, or toxicity of another drug. Drug Interaction,Interaction, Drug,Interactions, Drug
D005260 Female Females
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001522 Behavior, Animal The observable response an animal makes to any situation. Autotomy Animal,Animal Behavior,Animal Behaviors

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