Biomaterial Database

Changes in in vivo binding of 3H-Ro 15-1788 in mouse brain by reserpine. 1988

K Hashimoto, and O Inoue, and T Goromaru, and T Yamasaki

Department of Radiopharmaceutical Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences, University of Fukuyama, Japan.

The effects of reserpine on the in vivo binding of 3H-Ro 15-1788, (Ro 15-1788:ethyl 8-fluoro-5,6-dihydro-5-methyl-6-oxo-4H- imidazo[1,5a][1,4]benzodiazepine-3-carboxylate) a selective benzodiazepine antagonist, in the mouse brain were investigated. The biodistributions of tracer amounts of 3H-Ro 15-1788 in mice were significantly altered by pretreatment with reserpine (2.5 or 5.0 mg/kg, 24 h before the tracer administration). The time courses of radioactivity in the brain and the blood following i.v. injection of 3H-Ro 15-1788 with carrier Ro 15-1788 were not changed by pretreatment with reserpine, which suggested that the specific binding process might be altered by reserpine. The degree of alteration in the in vivo binding of 3H-Ro 15-1788 seemed to be dependent upon the dose of reserpine and the duration after the treatment of reserpine. The maximum changes in the biodistribution of 3H-Ro 15-1788 were observed at 1 day after injection of reserpine. The body temperature and the brain monoamine contents (dopamine, norepinephrine and 5-hydroxytryptamine) in mice were measured as indicators of pharmacological effects of reserpine, and good relationships to the degree of changes in the biodistribution of 3H-Ro 15-1788 and either the body temperature or brain monoamine contents, were observed. Furthermore, the changes in the biodistribution of 3H-Ro 15-1788 in the reserpinized mice were significantly suppressed by anti-depressant imipramine treatment. These results suggest that it would be possible to detect the in vivo drug interaction with brain benzodiazepine receptors in the living human brain using 11C-Ro 15-1788 and positron emission tomography (PET).

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
D012110	Reserpine	An alkaloid found in the roots of Rauwolfia serpentina and R. vomitoria. Reserpine inhibits the uptake of norepinephrine into storage vesicles resulting in depletion of catecholamines and serotonin from central and peripheral axon terminals. It has been used as an antihypertensive and an antipsychotic as well as a research tool, but its adverse effects limit its clinical use.	Raunervil,Raupasil,Rausedil,Rausedyl,Serpasil,Serpivite,V-Serp,V Serp
D001831	Body Temperature	The measure of the level of heat of a human or animal.	Organ Temperature,Body Temperatures,Organ Temperatures,Temperature, Body,Temperature, Organ,Temperatures, Body,Temperatures, Organ
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
D001923	Brain Chemistry	Changes in the amounts of various chemicals (neurotransmitters, receptors, enzymes, and other metabolites) specific to the area of the central nervous system contained within the head. These are monitored over time, during sensory stimulation, or under different disease states.	Chemistry, Brain,Brain Chemistries,Chemistries, Brain
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
D005442	Flumazenil	A potent benzodiazepine receptor antagonist. Since it reverses the sedative and other actions of benzodiazepines, it has been suggested as an antidote to benzodiazepine overdoses.	Flumazepil,Anexate,Lanexat,Ro 15-1788,Romazicon,Ro 15 1788,Ro 151788
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D012701	Serotonin	A biochemical messenger and regulator, synthesized from the essential amino acid L-TRYPTOPHAN. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (RECEPTORS, SEROTONIN) explain the broad physiological actions and distribution of this biochemical mediator.	5-HT,5-Hydroxytryptamine,3-(2-Aminoethyl)-1H-indol-5-ol,Enteramine,Hippophaine,Hydroxytryptamine,5 Hydroxytryptamine