ABSTRACT
Preclinical safety of reamberin, a preparation of succinic acid intended for the treatment of patients with shock conditions of different etiology, and remaxol a drug intended for the treatment of patients with liver dysfunction caused by acute intoxication was performed. Both medicines belong to the 5th class of practically non-toxic drugs. Their administration to experimental animals for 30 days did not cause toxic effects on the functional and morphological state of main systems and organs. Both medicines do not affect specific (humoral and cellular) and non-specific immune response and do not cause sensibilization, mutagenic, embryotoxic and teratogenic effects, and also do no alter parameters of reproductive functions of rats.
Subject(s)
Drug-Related Side Effects and Adverse Reactions , Meglumine/analogs & derivatives , Succinates/adverse effects , Succinates/pharmacology , Animals , Dogs , Drug Evaluation, Preclinical , Female , Male , Meglumine/adverse effects , Meglumine/pharmacology , Rats , Shock/drug therapyABSTRACT
We studied the functional role of individual subtypes of muscarinic cholinoceptors in the pathogenesis of neuroleptic parkinsonism in rats. Blockade of M4 receptors prevented the development of extrapyramidal disorders, which was abolished by simultaneous blockade of M2 receptors. The data suggest that various subtypes of muscarinic receptors are involved in the regulation of dopamine concentration.
Subject(s)
Catalepsy/etiology , Receptor, Muscarinic M2/antagonists & inhibitors , Receptor, Muscarinic M2/physiology , Animals , Catalepsy/chemically induced , Cyclopentanes/pharmacology , Diamines/pharmacology , Dopamine/metabolism , Haloperidol , Male , Mandelic Acids/pharmacology , Muscarinic Antagonists/pharmacology , Piperidines/pharmacology , Syndrome , Trihexyphenidyl/pharmacologyABSTRACT
We studied the relationship between the efficiency of muscarinic receptor antagonists in preventing haloperidol-induced catatonia and their activity in tests for the interaction of ligands with various subtypes of muscarinic receptors (M1-M4) in rats. Mathematical modeling showed that affinity of the ligand for M4 receptors positively affects its ability to correct extrapyramidal disorders (catatonic syndrome) produced by haloperidol, while affinity for M2 receptors had a negative effect on this characteristic.
Subject(s)
Catatonia/chemically induced , Catatonia/prevention & control , Haloperidol/toxicity , Receptor, Muscarinic M4/antagonists & inhibitors , Animals , Basal Ganglia Diseases/chemically induced , Basal Ganglia Diseases/metabolism , Basal Ganglia Diseases/prevention & control , Catatonia/metabolism , Kinetics , Ligands , Male , Models, Biological , Muscarinic Antagonists/pharmacology , Pilocarpine/pharmacology , Rats , Receptor, Muscarinic M4/metabolism , Receptors, Muscarinic/classification , Receptors, Muscarinic/metabolism , SyndromeABSTRACT
Correction of neuroleptic-induced parkinsonism in rats with two central cholinoblockers atropine and pentifine (acetylene aminoalcohol synthesized at Institute of Toxicology) were studied by measuring the content of acetylcholine in the striatum. The content of the transmitter secretion was estimated from the content of bound acetylcholine fraction in homogenates of the above-mentioned compartment of the brain. The results indicate that atropine and pentifine in doses equally effectively preventing catalepsy in rats had different effects on acetylcholine secretion in the striatum. Hence, cholinolytics with different pharmacological selective effects differently interact with central muscarine receptor subtypes.
Subject(s)
Acetylcholine/metabolism , Antipsychotic Agents/toxicity , Cholinergic Antagonists/pharmacology , Corpus Striatum/drug effects , Corpus Striatum/metabolism , Parkinsonian Disorders/drug therapy , Parkinsonian Disorders/metabolism , Animals , Atropine/pharmacology , Male , Parkinsonian Disorders/chemically induced , Rats , Receptors, Muscarinic/classification , Receptors, Muscarinic/drug effects , Receptors, Muscarinic/metabolismABSTRACT
In the in vitro experiments with hydrobiont Daphnia magna Straus as the test-object the comparative evaluation of the prooxydant activity of two neuroleptics galoperidol and aminazine, was performed. It was shown that galoperidol possesses the pronounced prooxydant activity compared with hydrogen peroxyde. Aminazine didn't display such an action. The exogenios reduced glutathione is capable to protect Daphnia from the prooxydant action of galoperidol may be used for the investigation of anti- and prooxydant effects of toxicants and medicines in vivo.
Subject(s)
Chlorpromazine/toxicity , Daphnia/drug effects , Haloperidol/toxicity , Oxidants/toxicity , Animals , Antioxidants/pharmacology , Hydrogen Peroxide/toxicity , Lethal Dose 50ABSTRACT
Pentifin and dopamine D1 receptor antagonist SCH-23390 possess similar pharmacological properties. In the present work we studied in vitro effects of Pentifin on dopamine receptors. Experiments on rat ductus deferents showed that Pentifin acts as a weak ligand of dopamine receptors. Our results indicate that the antihaloperidol effect of Pentifin is not related to the blockade of dopamine receptors.
Subject(s)
Amino Alcohols/pharmacology , Brain/drug effects , Brain/metabolism , Cyclopentanes/pharmacology , Piperidines/pharmacology , Receptors, Dopamine/metabolism , Amino Alcohols/chemistry , Amino Alcohols/metabolism , Amino Alcohols/therapeutic use , Animals , Cyclopentanes/chemistry , Cyclopentanes/metabolism , Cyclopentanes/therapeutic use , Dopamine Antagonists/chemistry , Dopamine Antagonists/metabolism , Dopamine Antagonists/pharmacology , Dopamine Antagonists/therapeutic use , In Vitro Techniques , Intestine, Small/drug effects , Male , Neurotransmitter Agents/metabolism , Parkinson Disease/drug therapy , Piperidines/chemistry , Piperidines/metabolism , Piperidines/therapeutic use , Rats , Seminal Vesicles/drug effects , Vas Deferens/drug effectsABSTRACT
Quantitative assessment of selective blockade of M4-subtype muscarinic receptors was performed by the number of pilocarpine-induced movements of lower jaw in rats. Three antagonists (atropine, cyclodol, and glipin) were used in the experiments. Glipin produced the most potent blockade of M4 receptors in the whole organism compared to other test antagonist.
Subject(s)
Motor Activity/drug effects , Muscarinic Antagonists/pharmacology , Receptor, Muscarinic M4/metabolism , Animals , Atropine/pharmacology , Dose-Response Relationship, Drug , Muscarinic Agonists/pharmacology , Pilocarpine/pharmacology , Rats , Trihexyphenidyl/pharmacology , Tropanes/pharmacologyABSTRACT
Mathematical analysis of the data obtained in experiments on the whole organism revealed that blockade of M(2)-cholinergic receptors increased both heart and respiratory rates. Blockade of M(1)-cholinergic receptors alleviated tachycardia induced by M(2)-receptor blockade.
