B-HT 920 (6-allyl-2-amino-5,6,7,8-tetrahydro-4H-thiazolo[4,5-d]azepine), a candidate for selective dopamine (DA) autoreceptor agonist activity, was tested for its interactions with biochemical parameters of brain dopaminergic, noradrenergic and serotoninergic systems as measured in ventriculocisternal perfusates of chloralose-anaesthetized cats. DA, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), noradrenaline (NA) and 5-hydroxyindolic acid (5-HIAA) were measured in samples of 30 min collection periods by high-pressure liquid chromatography with electrochemical detection. B-HT 920, in the dose range of 0.03-1 mg/kg i.v., promptly inhibited the efflux of DA and DOPAC in a dose-dependent manner. The 1 mg/kg dose of B-HT 920 reduced the DA levels below 25% of control levels for the whole length of the experiments. The HVA levels were reduced less and in a protracted manner. Only the highest dose of B-HT 920 tested (1 mg/kg) had a significant effect on the level of NA (marked, prompt reduction) and 5-HIAA (delayed, moderate reduction), reflecting its well known alpha 2-adrenoceptor agonist property. The effects of B-HT 920 on the dopaminergic indices were DA receptor-mediated as they were reversed by a low dose (0.05 mg/kg i.v.) of haloperidol. In contrast, the alpha 2-adrenoceptor blocking drug, idazoxan, 4 mg/kg i.v., while it reversed the NA and 5-HIAA reductions did not modify the effect of B-HT 920 on DA, DOPAC and HVA. Thus B-HT 920, in the dose range between 0.03-0.1 mg/kg, selectively affected brain dopaminergic parameters. Our experiments demonstrated that B-HT 920 causes an effective, long lasting and selective suppression of extracellular brain DA levels in vivo. B-HT 920 represents a promising compound for clinical use in pathological conditions known to be ameliorated by a reduction of brain DA activity, such as Huntington's disease, mania and schizophrenia.
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http://dx.doi.org/10.1016/0014-2999(88)90585-7 | DOI Listing |
Neuroreport
December 2015
Central Research Laboratory, Kissei Pharmaceutical Co. Ltd, Azumino, Nagano, Japan.
Although 6-hydroxydopamine-induced (6-OHDA-induced) rats are a well-known Parkinson's disease model, the effects of dopamine D2 agonists in mice with 6-OHDA-induced lesions are not completely understood. We produced mice with 6-OHDA-induced lesions and measured their total locomotion counts following administration of several dopamine D2 agonists (pramipexole, ropinirole, cabergoline, rotigotine, apomorphine, talipexole, and quinelorane). Cabergoline showed the longest duration of drug action, which was in agreement with its long-lived anti-Parkinson effects in rats and humans.
View Article and Find Full Text PDFNihon Shinkei Seishin Yakurigaku Zasshi
November 2014
This review discusses the relationship between therapeutic plasma concentrations of antiparkinson dopamine agonists (rotigotine, pergolide, cabergoline, apomorphine, bromocriptine, ropinirole, pramipexole, and talipexole) and their in vitro pharmacology at dopamine D1, D2 and D3 receptors. A significant correlation was found between therapeutic plasma concentrations of these dopamine agonists and their agonist potencies (EC50) at D2 receptors, although no such correlation existed at D1 or D3 receptors, suggesting that D2 receptors could be the primary and common target for the antiparkinson action of all dopamine agonists. However, D1 receptor stimulation is also important for maintaining swallowing reflex, bladder function and cognition.
View Article and Find Full Text PDFNeurol Sci
June 2015
Department of Neurology, Juntendo University, School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, Japan,
Hum Fertil (Camb)
September 2013
University of Nottingham - NURTURE, Queen's Medical Centre, Nottingham , UK.
Controlled ovarian stimulation is an integral part of assisted reproduction treatment. This can result in ovarian hyperstimulation syndrome (OHSS), which is associated with significant morbidity and potentially mortality. Recent approaches to ovarian stimulation have led to a reduction in the prevalence of OHSS but it still occurs.
View Article and Find Full Text PDFPathobiology
May 2014
Molecular Pathology, Biotech Research and Innovation Centre, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Objectives: Hypothermia is still unproven as beneficial treatment in human stroke, although in animal models, conditioning the brain with hypothermia has induced tolerance to insults. Here, we delineate the feasibility of drug-induced mild hypothermia in reducing ischemic brain damage when conditioning before (preconditioning) and after (postconditioning) experimental stroke.
Methods: Hypothermia was induced in rats with a bolus of 6 mg/kg talipexole followed by 20 h continuous talipexole infusion of 6 mg/kg in total.
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