Biomaterial Database

Some central effects of CGP 37849 and CGP 39551, the competitive NMDA receptor antagonists: potential antiparkinsonian activity. 1993

J Maj, and G Skuza, and Z Rogóz

Institute of Pharmacology, Polish Academy of Sciences, Kraków.

Two new competitive NMDA receptor antagonists with oral activity CGP 37849 (D,L-E-amino-methyl-phosphono-3-pentenoic acid) and its ethyl ester CGP 39551 were studied in rats. CGP 37849 did not change the locomotor activity or increased it. The hyperactivity induced by CGP 37849 was antagonized by haloperidol but not idazoxan or prazosin. CGP 39551 decreased the locomotor activity. The studied compounds did not increase the locomotion in monoamine-depleted (pretreated with reserpine and alpha-methyl-p-tyrosine) rats. Clonidine induced antiakinetic effect in monoamine-depleted rats. This effect was more pronounced after joint administration of clonidine and CGP 37849 or CGP 39551. The locomotor hyperactivity induced by joint administration of CGP 37849 and clonidine was inhibited by haloperidol but not prazosin or idazoxan. CGP 37849 but not CGP 39551 also enhanced antiakinetic effect of L-DOPA (given together with benserazide) in monoamine-depleted rats. CGP 37849 antagonized the spiperone- and fluphenazine-induced catalepsy; CGP 39551 had considerably weaker antagonistic effect. The reserpine-induced catalepsy was attenuated by CGP 37849. MK-801, a non-competitive NMDA antagonist inhibited spiperone- but not reserpine-induced catalepsy. The obtained results indicate that CGP 37849 administered alone or in combination with L-DOPA or clonidine may be a potential antiparkinsonian drug.

UI	MeSH Term	Description	Entries
D007980	Levodopa	The naturally occurring form of DIHYDROXYPHENYLALANINE and the immediate precursor of DOPAMINE. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to DOPAMINE. It is used for the treatment of PARKINSONIAN DISORDERS and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system.	L-Dopa,3-Hydroxy-L-tyrosine,Dopaflex,Dopar,L-3,4-Dihydroxyphenylalanine,Larodopa,Levopa,3 Hydroxy L tyrosine,L 3,4 Dihydroxyphenylalanine,L Dopa
D008297	Male		Males
D008781	Methyltyrosines	A group of compounds that are methyl derivatives of the amino acid TYROSINE.
D009043	Motor Activity	Body movements of a human or an animal as a behavioral phenomenon.	Activities, Motor,Activity, Motor,Motor Activities
D012110	Reserpine	An alkaloid found in the roots of Rauwolfia serpentina and R. vomitoria. Reserpine inhibits the uptake of norepinephrine into storage vesicles resulting in depletion of catecholamines and serotonin from central and peripheral axon terminals. It has been used as an antihypertensive and an antipsychotic as well as a research tool, but its adverse effects limit its clinical use.	Raunervil,Raupasil,Rausedil,Rausedyl,Serpasil,Serpivite,V-Serp,V Serp
D002375	Catalepsy	A condition characterized by inactivity, decreased responsiveness to stimuli, and a tendency to maintain an immobile posture. The limbs tend to remain in whatever position they are placed (waxy flexibility). Catalepsy may be associated with PSYCHOTIC DISORDERS (e.g., SCHIZOPHRENIA, CATATONIC), nervous system drug toxicity, and other conditions.	Cerea Flexibilitas,Flexibility, Waxy,Anochlesia,Anochlesias,Catalepsies,Flexibilitas, Cerea,Flexibilities, Waxy,Waxy Flexibilities,Waxy Flexibility
D002491	Central Nervous System Agents	A class of drugs producing both physiological and psychological effects through a variety of mechanisms. They can be divided into "specific" agents, e.g., affecting an identifiable molecular mechanism unique to target cells bearing receptors for that agent, and "nonspecific" agents, those producing effects on different target cells and acting by diverse molecular mechanisms. Those with nonspecific mechanisms are generally further classed according to whether they produce behavioral depression or stimulation. Those with specific mechanisms are classed by locus of action or specific therapeutic use. (From Gilman AG, et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed, p252)	Central Nervous System Drugs
D003000	Clonidine	An imidazoline sympatholytic agent that stimulates ALPHA-2 ADRENERGIC RECEPTORS and central IMIDAZOLINE RECEPTORS. It is commonly used in the management of HYPERTENSION.	Catapres,Catapresan,Catapressan,Chlophazolin,Clofelin,Clofenil,Clonidine Dihydrochloride,Clonidine Hydrochloride,Clonidine Monohydrobromide,Clonidine Monohydrochloride,Clopheline,Dixarit,Gemiton,Hemiton,Isoglaucon,Klofelin,Klofenil,M-5041T,ST-155,Dihydrochloride, Clonidine,Hydrochloride, Clonidine,M 5041T,M5041T,Monohydrobromide, Clonidine,Monohydrochloride, Clonidine,ST 155,ST155
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
D000978	Antiparkinson Agents	Agents used in the treatment of Parkinson's disease. The most commonly used drugs act on the dopaminergic system in the striatum and basal ganglia or are centrally acting muscarinic antagonists.	Antiparkinson Drugs,Antiparkinsonian Agents,Antiparkinsonians,Agents, Antiparkinson,Agents, Antiparkinsonian,Drugs, Antiparkinson