Biomaterial Database

The dopamine autoreceptor agonist, B-HT 920, preferentially reduces brain dopamine release in vivo: biochemical indices of brain dopamine, noradrenaline and serotonin in ventriculocisternal perfusates in the cat. 1988

C Pifl, and L Pichler, and W Kobinger, and O Hornykiewicz

Institute of Biochemical Pharmacology, University of Vienna, Austria.

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.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D009638	Norepinephrine	Precursor of epinephrine that is secreted by the ADRENAL MEDULLA and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the LOCUS CERULEUS. It is also found in plants and is used pharmacologically as a sympathomimetic.	Levarterenol,Levonorepinephrine,Noradrenaline,Arterenol,Levonor,Levophed,Levophed Bitartrate,Noradrenaline Bitartrate,Noradrénaline tartrate renaudin,Norepinephrin d-Tartrate (1:1),Norepinephrine Bitartrate,Norepinephrine Hydrochloride,Norepinephrine Hydrochloride, (+)-Isomer,Norepinephrine Hydrochloride, (+,-)-Isomer,Norepinephrine d-Tartrate (1:1),Norepinephrine l-Tartrate (1:1),Norepinephrine l-Tartrate (1:1), (+,-)-Isomer,Norepinephrine l-Tartrate (1:1), Monohydrate,Norepinephrine l-Tartrate (1:1), Monohydrate, (+)-Isomer,Norepinephrine l-Tartrate (1:2),Norepinephrine l-Tartrate, (+)-Isomer,Norepinephrine, (+)-Isomer,Norepinephrine, (+,-)-Isomer
D001921	Brain	The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.	Encephalon
D002415	Cats	The domestic cat, Felis catus, of the carnivore family FELIDAE, comprising over 30 different breeds. The domestic cat is descended primarily from the wild cat of Africa and extreme southwestern Asia. Though probably present in towns in Palestine as long ago as 7000 years, actual domestication occurred in Egypt about 4000 years ago. (From Walker's Mammals of the World, 6th ed, p801)	Felis catus,Felis domesticus,Domestic Cats,Felis domestica,Felis sylvestris catus,Cat,Cat, Domestic,Cats, Domestic,Domestic Cat
D002552	Cerebral Ventricles	Four CSF-filled (see CEREBROSPINAL FLUID) cavities within the cerebral hemispheres (LATERAL VENTRICLES), in the midline (THIRD VENTRICLE) and within the PONS and MEDULLA OBLONGATA (FOURTH VENTRICLE).	Foramen of Monro,Cerebral Ventricular System,Cerebral Ventricle,Cerebral Ventricular Systems,Monro Foramen,System, Cerebral Ventricular,Systems, Cerebral Ventricular,Ventricle, Cerebral,Ventricles, Cerebral,Ventricular System, Cerebral,Ventricular Systems, Cerebral
D002946	Cisterna Magna	One of three principal openings in the SUBARACHNOID SPACE. They are also known as cerebellomedullary cistern, and collectively as cisterns.	Magna, Cisterna
D004146	Dioxanes	Compounds that contain the structure 1,4-dioxane.
D004298	Dopamine	One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.	Hydroxytyramine,3,4-Dihydroxyphenethylamine,4-(2-Aminoethyl)-1,2-benzenediol,Dopamine Hydrochloride,Intropin,3,4 Dihydroxyphenethylamine,Hydrochloride, Dopamine
D005260	Female		Females
D006220	Haloperidol	A phenyl-piperidinyl-butyrophenone that is used primarily to treat SCHIZOPHRENIA and other PSYCHOSES. It is also used in schizoaffective disorder, DELUSIONAL DISORDERS, ballism, and TOURETTE SYNDROME (a drug of choice) and occasionally as adjunctive therapy in INTELLECTUAL DISABILITY and the chorea of HUNTINGTON DISEASE. It is a potent antiemetic and is used in the treatment of intractable HICCUPS. (From AMA Drug Evaluations Annual, 1994, p279)	Haldol