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Titolo:
Cerebral glucose metabolic and plasma catecholamine responses to the alpha(2) adrenoceptor antagonist ethoxyidazoxan given to healthy volunteers
Autore:
Schmidt, ME; Oshinsky, RJ; Kim, HG; Schouten, JL; Folley, BS; Potter, WZ;
Indirizzi:
Eli Lilly & Co, Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USAEli Lilly & Co Indianapolis IN USA 46285 Labs, Indianapolis, IN 46285 USA NIMH, Clin Pharmacol Sect, Bethesda, MD 20892 USA NIMH Bethesda MD USA 20892 H, Clin Pharmacol Sect, Bethesda, MD 20892 USA Allegheny Univ Hlth Sci, Dept Neurol, Philadelphia, PA 19129 USA AlleghenyUniv Hlth Sci Philadelphia PA USA 19129 ladelphia, PA 19129 USA Dankook Univ, Dept Pharmacol, Choongnam 330714, South Korea Dankook Univ Choongnam South Korea 330714 Choongnam 330714, South Korea NIMH, LBC, Sect Funct Brain Imaging, Bethesda, MD 20892 USA NIMH BethesdaMD USA 20892 ct Funct Brain Imaging, Bethesda, MD 20892 USA Kennedy Krieger Inst, Neuroimaging Res Ctr, Baltimore, MD 21205 USA Kennedy Krieger Inst Baltimore MD USA 21205 Ctr, Baltimore, MD 21205 USA
Titolo Testata:
PSYCHOPHARMACOLOGY
fascicolo: 2, volume: 146, anno: 1999,
pagine: 119 - 127
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN BRAIN; ALPHA(2)-ADRENOCEPTOR BLOCKADE; PREFRONTAL CORTEX; BINDING-SITES; TEST-RETEST; RAT-BRAIN; IDAZOXAN; ALPHA-2-ADRENOCEPTORS; LOCALIZATION; NOREPINEPHRINE;
Keywords:
alpha(2)-adrenoceptor; imidazoline; cerebral glucose metabolic rate; catecholamine;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
48
Recensione:
Indirizzi per estratti:
Indirizzo: Schmidt, ME Eli Lilly & Co, Lilly Corp Ctr, Lilly Res Labs, DC 0532, Indianapolis, IN 46285 USA Eli Lilly & Co DC 0532 Indianapolis IN USA 46285 IN 46285 USA
Citazione:
M.E. Schmidt et al., "Cerebral glucose metabolic and plasma catecholamine responses to the alpha(2) adrenoceptor antagonist ethoxyidazoxan given to healthy volunteers", PSYCHOPHAR, 146(2), 1999, pp. 119-127

Abstract

Rationale: Methods that test for the central effects of alpha(2)-adrenoceptor antagonists can facilitate the clinical development of such compounds. Recently we evaluated the effects of idazoxan (IDX), an alpha(2)-adrenoceptor antagonist with high affinity for imidazoline sites, on a variety of measures potentially sensitive to blockade of alpha(2)-adrenoceptors includingregional brain glucose metabolic rate. Objective: To test whether these effects on brain metabolic rate could have been mediated by imidazoline binding sites, single dose challenges of 9 or 12 mcg/kg ethoxyidazoxan (ETX; an alpha(2)-adrenoceptor antagonist which does not bind to imidazoline sites) were given to healthy male volunteers. Methods: The effects on brain glucose metabolism, blood pressure, catecholamines, and behavior were assessed. Results: Blood pressure increased 10-15% after both doses, Plasma catecholamines increased 2- to 2.5-fold and responses were dose dependent. There was no evidence of either dose being anxiogenic. Both doses of ETX produced diffuse increases in brain glucose metabolism. Conclusions: Brain glucose metabolic responses were more widespread and monotonic than we had observed with IDX. ETX also produced robust increases in glucose metabolism in cerebellum. While we were unable to exclude the possibility that some of the brain metabolic responses we had observed with IDX were mediated by imidazoline sites, ETX may be sufficiently distinct from IDX in alpha(2)-adrenoceptor affinity that differences in acute metabolic responses occurred.

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Documento generato il 06/04/20 alle ore 05:43:22