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Titolo:
Attenuation of the neuropsychiatric effects of ketamine with lamotrigine -Support for hyperglutamatergic effects of N-methyl-D-aspartate receptor antagonists
Autore:
Anand, A; Charney, DS; Oren, DA; Berman, RM; Hu, XS; Cappiello, A; Krystal, JH;
Indirizzi:
Yale Univ, Sch Med, Dept Psychiat, VA Connecticut Healthcare Syst, W Haven, CT 06516 USA Yale Univ W Haven CT USA 06516 cut Healthcare Syst, W Haven, CT 06516 USA Connecticut Mental Hlth Ctr, Abraham Ribicoff Res Facil, New Haven, CT 06519 USA Connecticut Mental Hlth Ctr New Haven CT USA 06519 ew Haven, CT 06519 USA
Titolo Testata:
ARCHIVES OF GENERAL PSYCHIATRY
fascicolo: 3, volume: 57, anno: 2000,
pagine: 270 - 276
SICI:
0003-990X(200003)57:3<270:AOTNEO>2.0.ZU;2-W
Fonte:
ISI
Lingua:
ENG
Soggetto:
CEREBELLAR GRANULE CELLS; HEALTHY-VOLUNTEERS; GLUTAMATE RELEASE; NMDA ANTAGONIST; SCHIZOPHRENIA; RATS; INHIBITION; PSYCHOSIS; BW619C89; AGONIST;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Social & Behavioral Sciences
Clinical Medicine
Life Sciences
Citazioni:
53
Recensione:
Indirizzi per estratti:
Indirizzo: Anand, A Yale Univ, Sch Med, Dept Psychiat, VA Connecticut Healthcare Syst, Mail Stop 116A, W Haven, CT 06516 USA Yale Univ Mail Stop 116A W Haven CTUSA 06516 Haven, CT 06516 USA
Citazione:
A. Anand et al., "Attenuation of the neuropsychiatric effects of ketamine with lamotrigine -Support for hyperglutamatergic effects of N-methyl-D-aspartate receptor antagonists", ARCH G PSYC, 57(3), 2000, pp. 270-276

Abstract

Background: The cognitive, behavioral, and mood effects of N-methyl-D-aspartate (NMDA) receptor antagonists, such as phencyclidine and ketamine, havebeen used to study the effects of NMDA receptor dysfunction. Pharmacological modulation of the effects of NMDA receptor antagonists, such as ketamine, may lead to development of novel therapeutic agents for psychiatric illnesses such as schizophrenia. Preclinical studies indicate that some ketamineeffects may be mediated through increased glutamate release. In this study, we tested the hypothesis that lamotrigine, a drug reported to inhibit glutamate release, will reduce the neuropsychiatric effects of ketamine in humans. Method: Healthy subjects (n = 16) completed 4 test days involving the administration of lamotrigine, 300 mg by mouth, or placebo 2 hours prior to administration of ketamine (0.26 mg/kg by intravenous bolus and 0.65 mg/kg perhour by intravenous infusion) or placebo in a randomized order under double-blind conditions. Behavioral and cognitive assessments were performed at baseline and after administration of the medications. Results: Lamotrigine significantly decreased ketamine-induced perceptual abnormalities as assessed by the Clinician;Administered Dissociative States Scale (P<.001); positive symptoms of schizophrenia as assessed by the BriefPsychiatric Rating Scale positive symptoms subscale (P<.001); negative symptoms as assessed by the Brief Psychiatric Rating Scale negative symptoms subscale (P<.05); and learning and memory impairment as assessed by the Hopkins Verbal Learning Test (P<.05). However, lamotrigine increased the immediate mood-elevating effects of ketamine (P<.05). Conclusions: Glutamate release-inhibiting drugs may reduce the hyperglutamatergic consequences of NMDA receptor dysfunction implicated in the pathophysiologic processes of neuropsychiatric illnesses such as schizophrenia. Further study is needed.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 22/01/20 alle ore 12:58:50