ABSTRACT
The effects of the new structural analogue of benactyzine, a derivative of fluorencarbonic acid, on monoamine levels in brain structures were studied in male Wistar rats with experimental depression. Depressive state in rats was modeled by single injection of reserpine (4 mg/kg). The concentrations of norepinephrine (NE), dopamine (DA), serotonin (5-HT), and their metabolites 3,4-dihydroxyphenylacetic acid (DOPAC), homovanilic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) in the hypothalamus and striatum were measured by HPLC. It was found that preliminary treatment (30 days) with the derivative of fluorencarbonic acid prevented a decrease in monoamine level in the hypothalamus (NE, 5-HT, and 5-HIAA) and striatum (DA, 5-HT, and 5-HIAA). The neurochemical shifts (correction of 5-HT deficiency and stabilization of DA and NE levels) correlated with the high antidepressant activity of this agent observed in Porsolt forced swimming test.
Subject(s)
Biogenic Monoamines/metabolism , Brain/metabolism , Depression/metabolism , 3,4-Dihydroxyphenylacetic Acid/metabolism , Animals , Chromatography, High Pressure Liquid , Dopamine/metabolism , Homovanillic Acid/metabolism , Hypothalamus/metabolism , Male , Norepinephrine/metabolism , Rats , Rats, Wistar , Serotonin/metabolismABSTRACT
The present report describes development of hexamethonium complexes based on fullerene C60. Hexamethonium has a limited penetration into CNS and therefore can antagonize central effects of nicotine only when given at high doses. In the present studies conducted in laboratory rodents, intraperitoneal administration of hexamethonium-fullerene complexes blocked effects of nicotine (convulsions and locomotor stimulation). When compared to equimolar doses of hexamethonium, complexes of hexamethonium with derivatives of fullerene C60 were 40 times more potent indicating an enhanced ability to interact with central nicotine receptors. Thus, fullerene C60 derivatives should be explored further as potential carrier systems for polar drug delivery into CNS.
Subject(s)
Brain/drug effects , Fullerenes/pharmacokinetics , Hexamethonium Compounds/pharmacokinetics , Nicotinic Antagonists/pharmacokinetics , Aminocaproates/chemistry , Animals , Anticonvulsants/chemistry , Anticonvulsants/pharmacokinetics , Brain/metabolism , Dose-Response Relationship, Drug , Fullerenes/administration & dosage , Fullerenes/chemistry , Hexamethonium Compounds/administration & dosage , Hexamethonium Compounds/chemistry , Locomotion/drug effects , Male , Mice , Nicotine , Nicotinic Antagonists/administration & dosage , Nicotinic Antagonists/chemistry , Rats, Wistar , Seizures/drug therapyABSTRACT
We have found that N-cholinolytic drug benzohexonium produces a hypolipidemic effect: it reduces dyslipoproteinemia, fatty infiltration of the liver, and risk of atherosclerotic lesions.
