Nitric oxide (NO) pathway and locomotor hyperactivity towards dopaminomimetics in rats. 1997

E Przegaliński, and M Filip
Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.

The effects of the NO donor molsidomine and the inhibitors of the NO synthase (NOS) 7-nitroindazole (7-NI) and NG-nitro-L-arginine methyl ester (L-NAME) on the motor hyperactivity induced by indirect (amphetamine and cocaine) or direct (SKF 38393 and bromocriptine) dopamine (DA) agonists were studied in rats. The hyperactivity induced by 0.5 mg/kg of amphetamine or 5 mg/kg of cocaine was potentiated in a dose-dependent manner by molsidomine (30-100 mg/kg), but attenuated by 7-NI (3-30 mg/kg) or L-NAME (3-30 mg/kg). The NOS inhibitors also inhibited the locomotor hyperactivity evoked by 15 mg/kg of SKF 38393 (a DA D1 agonist) or 5 mg/kg of bromocriptine (a DA D2 agonist). On the other hand, the hyperactivity induced by those direct DA receptor agonists was potentiated by molsidomine. The present findings provide further evidence for an interaction at the behavioral level between NO and the DA-mediated effects of amphetamine and cocaine; moreover, they seem to indicate that both DA D1 and DA D2 receptor subtypes are under such influence.

UI MeSH Term Description Entries
D007191 Indazoles A group of heterocyclic aromatic organic compounds consisting of the fusion of BENZENE and PYRAZOLES. Indazole
D008297 Male Males
D008981 Molsidomine A morpholinyl sydnone imine ethyl ester, having a nitrogen in place of the keto oxygen. It acts as NITRIC OXIDE DONORS and is a vasodilator that has been used in ANGINA PECTORIS. Morsydomine,Corpea,Corvaton,Duracoron,Fali-Cor,Korvatone,MTW-Molsidomin,Molsi 1A Pharma,Molsi-AZU,Molsi-Puren,Molsibeta,Molsicor,Molsidain,Molsidomin,Molsidomin Heumann,Molsidomin Stada,Molsidomin Von Ct,Molsidomin-Ratiopharm,Molsihexal,Molsiket,SIN-10,Sydnopharm,Fali Cor,Heumann, Molsidomin,MTW Molsidomin,Molsi AZU,Molsi Puren,Molsidomin Ratiopharm,SIN 10,SIN10,Von Ct, Molsidomin
D009043 Motor Activity Body movements of a human or an animal as a behavioral phenomenon. Activities, Motor,Activity, Motor,Motor Activities
D009569 Nitric Oxide A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP. Endogenous Nitrate Vasodilator,Mononitrogen Monoxide,Nitric Oxide, Endothelium-Derived,Nitrogen Monoxide,Endothelium-Derived Nitric Oxide,Monoxide, Mononitrogen,Monoxide, Nitrogen,Nitrate Vasodilator, Endogenous,Nitric Oxide, Endothelium Derived,Oxide, Nitric,Vasodilator, Endogenous Nitrate
D001971 Bromocriptine A semisynthetic ergotamine alkaloid that is a dopamine D2 agonist. It suppresses prolactin secretion. 2-Bromoergocryptine,Bromocryptin,2-Bromo-alpha-ergocryptine,2-Bromo-alpha-ergokryptine,2-Bromoergocryptine Mesylate,2-Bromoergocryptine Methanesulfonate,2-Bromoergokryptine,Bromocriptin,Bromocriptine Mesylate,CB-154,Parlodel,2 Bromo alpha ergocryptine,2 Bromo alpha ergokryptine,2 Bromoergocryptine,2 Bromoergocryptine Mesylate,2 Bromoergocryptine Methanesulfonate,2 Bromoergokryptine,CB 154,CB154,Mesylate, 2-Bromoergocryptine,Mesylate, Bromocriptine,Methanesulfonate, 2-Bromoergocryptine
D003042 Cocaine An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. Cocaine HCl,Cocaine Hydrochloride,HCl, Cocaine,Hydrochloride, Cocaine
D004791 Enzyme Inhibitors Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D006948 Hyperkinesis Excessive movement of muscles of the body as a whole, which may be associated with organic or psychological disorders. Hyperactivity, Motor,Hyperkinesia,Hyperkinesia, Generalized,Hyperkinetic Movements,Generalized Hyperkinesia,Generalized Hyperkinesias,Hyperkinesias, Generalized,Hyperkinetic Movement,Motor Hyperactivity,Movement, Hyperkinetic,Movements, Hyperkinetic
D000661 Amphetamine A powerful central nervous system stimulant and sympathomimetic. Amphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulation of release of monamines, and inhibiting monoamine oxidase. Amphetamine is also a drug of abuse and a psychotomimetic. The l- and the d,l-forms are included here. The l-form has less central nervous system activity but stronger cardiovascular effects. The d-form is DEXTROAMPHETAMINE. Desoxynorephedrin,Levoamphetamine,Phenopromin,l-Amphetamine,Amfetamine,Amphetamine Sulfate,Amphetamine Sulfate (2:1),Centramina,Fenamine,Mydrial,Phenamine,Thyramine,levo-Amphetamine,Sulfate, Amphetamine,l Amphetamine,levo Amphetamine

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