Effect of bromantane, a new immunostimulating agent with psychostimulating activity, on the release and metabolism of dopamine in the striatum of freely moving rats. A microdialysis study

Abstract

It is demonstrated that bromantane induces a pronounced and prolonged (8 h) increase in the release of dopanime. Tetrodotoxin (10 .6 M) perfused via a microdialysis probe partially inhibits the bromantane-induced release of dopamine. The extracellular content of the dopamine metabolites 3,4-dioxyphenylacetic and homovanillic acids is slightly decreased. The possible mechanisms of action of bromantane on the dopamin-and serotoninergic systems of the brain are discussed.Key Words: psychostimulators; bromantane; dopamine, striatum, microdialysisis a new immunostimulating drug [3] with psychoactivating and adaptogenic properties [5][6][7]. Its mechanism of action has not been studied in sufficient detail. The dopaminergic and serotoninergic systems play an important role in the realization of the effects of adamantane derivatives [1,2,4,8,11,12,14]. In a concentration range of 50-500 ~M bromantane notably reduces serotonin reuptake by rat brain synaptosomes, inhibiting to a lesser exteat the reuptake of dopamine. The fact that bromantane eliminates catalepsy induced by haloperidol and tryphtazin indicates that the dopaminand serotoninergic brain structures play an instrumental role in the the pharmacological effect of bromantane. From this viewpoint, a detailed examination of the effect of bromantane on the function of these two neurotransmitter brain systems is of undoubted interest.Our objective was to examine the effect of bromantane on the release of dopamine and to measure by intracerebral dialysis the extracellular content of the bromantane metabolites 3,4-dihydroxyphenylacetic and homovanillic acids, DOPAC and HVA, in the dorsal striatum of the brain of freely moving rats [10]. The method of intracerebral dialysis makes it possible to evaluate the state of a particular neurotransmitter system while preserving the brain neuroregulatory mechanisms. MATERIALS AND METHODSExperiments were performed on male Wistar rats weighing 200-250 g. The animals were anesthetized with chloralhydrate (400 mg/kg intraperitoneally) and were placed in a stereotaxic apparatus (David Kopf Instruments). A dialysis membrane (the length of membrane exposure relative to the bregma was 10 ram, outer diameter was 0.32 ram,

History of Doping and Doping Control

“…Most newer doping agents of lower molecular size (below 1000 Da) can be included into the normal scheme of GC-MS or LC-MS procedures without great difficulty, and have sometimes been detected even if completely unused and more or less unknown, and have afterwards been explicitly included in the Prohibited List, e.g. clenbuterol 1992 (Maltin et al 1987a, b); bromantane 1994 (Badyshtov et al 1995;Bumat et al 1997;Grekhova et al 1995;Kudrin et al 1995); carphedone or phenylpiracetam 1996 (Müller et al 1999;Kim et al 1999 For the peptide and glycoproteine hormones (with much larger molecules between 10 3 and 10 5 Da and with many different chemical properties), immunoassays -partly combined with electrochemical separation -as well as an "indirect approach" have been introduced. The direct approach identifies the hormone itself (and has to distinguish the exogenous product from the physiological one), while the indirect principle quantifies and evaluates parameters which are physiologically correlated with the hormone (such as erythropoietin haemoglobin or hematocrit, ferritin, soluble transferrin receptor, reticulocytes) (Catlin et al 2002;Gore et al 2003;Lasne 2001;Lasne and de Ceaurriz 2000;Lasne et al 2002;Parisotto et al 2000Parisotto et al , 2001.…”

Effects of the Novel Anti-Asthenic Drug Ladasten on Behavior and T-Cell Subsets Alterations in a Social Defeat Animal Model of Depression

“…This de novo synthesis of catecholamines is regarded as the key mechanism of the psychotropic activity of ladasten [16,18,19]. Early studies demonstrated that ladasten exerts central dopaminomimetic effects which were related to DA release from the pre-synaptic endings of free-moving rats [20,21]. In vitro experiments have shown that 50 -500 μkM ladasten significantly decreases the uptake of serotonin by the isolated cerebral synaptosomes of rats and, to a lesser degree, inhibits the uptake of dopamine [22].…”

A Rapid and Sensitive LC–MS/MS Assay for the Quantitation of Bromantane in Human Plasma

“…Bromantane, N-(4-bromophenyl) adamantan-2-amine, is a drug with anxiolytic and immunostimulatory actions and elements of actoprotective activity [1][2][3]. Bromantane is not potentially addictive and does not exert effects of hypnosedation or neuromuscular relaxation.…”