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Titolo:
GYKI-52466 AND RELATED 2,3-BENZODIAZEPINES AS ANTICONVULSANT AGENTS IN DBA 2 MICE/
Autore:
DESARRO G; CHIMIRRI A; DESARRO A; GITTO R; GRASSO S; GIUSTI P; CHAPMAN AG;
Indirizzi:
UNIV MESSINA,SCH MED,INST PHARMACOL,CHAIR CHEMOTHERAPY,PIAZZA XX SETTEMBRE 4 I-98122 MESSINA ITALY UNIV MESSINA,SCH MED,INST PHARMACOL,CHAIR CHEMOTHERAPY I-98122 MESSINA ITALY UNIV REGGIO CALABRIA,SCH MED,DEPT EXPTL & CLIN MED,CHAIR PHARMACOL I-89100 REGGIO CALABRIA ITALY UNIV MESSINA,SCH PHARM,DEPT MED CHEM MESSINA ITALY UNIV PADUA,SCH MED,DEPT PHARMACOL PADUA ITALY UNIV LONDON,INST PSYCHIAT,DEPT NEUROL LONDON SE5 8AF ENGLAND
Titolo Testata:
European journal of pharmacology
fascicolo: 2-3, volume: 294, anno: 1995,
pagine: 411 - 422
SICI:
0014-2999(1995)294:2-3<411:GAR2AA>2.0.ZU;2-B
Fonte:
ISI
Lingua:
ENG
Soggetto:
NMDA GLUTAMATE RECEPTOR; D-ASPARTATE RECEPTOR; EPILEPSY-PRONE RATS; QUISQUALATE RECEPTORS; REFLEX EPILEPSY; ANTAGONISTS; GYKI-52466; MODELS; NBQX; ACID;
Keywords:
2,3-BENZODIAZEPINE; GYKI 52466; ANIRACETAM; AMPA LPHA-AMINO-3-HYDROXY-5-METHYL-4-ISOXAZOLEPROPIONIC ACID) ANTICONVULSANT DRUG; EPILEPSY; AUDIOGENIC SEIZURE; (DBA/2 MOUSE);
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
52
Recensione:
Indirizzi per estratti:
Citazione:
G. Desarro et al., "GYKI-52466 AND RELATED 2,3-BENZODIAZEPINES AS ANTICONVULSANT AGENTS IN DBA 2 MICE/", European journal of pharmacology, 294(2-3), 1995, pp. 411-422

Abstract

The behavioural and anticonvulsant effects of several 1-aryl-3,5-dihydro-4H-2,3-benzodiazepin-4-ones (2,3-BZs) and of l[1,2,4]oxadiazolo[5,4-a][2,3]benzodiazepin-6-ones (2,3-OBZs) were studied after intraperitoneal (i.p.) administration in DBA/2 mice, a strain genetically susceptible to sound-induced seizures. The seizures were evoked by means of auditory stimulation (109 dB, 12-16 kHz) in animals placed singly under a hemispheric Perspex dome. The 2,3-benzodiazepines studied after 30min pretreatment were generally less potent than the related derivative 1-(4-aminophenyl)4-methyl-7,8-methylene dioxy-5H-2,3-benzodiazepinehydrochloride (GYKI 52466) except -7,8-dimethoxy-1-phenyl-4H-2,3-benzodiazepin-4-one (2,3-BZ-2) and 2,3-BZ-2M (3-methyl derivative of 2,3-BZ-2) which showed comparable activity. Thirty minutes after i.p. administration of 2,3-benzodiazepines, the rank order of potency for anticonvulsant activity against clonus was 2,3-BZ-2 > GYKI 52466 > 2,3BZ-2M > 2,3-BZ-1 > 2,3-BZ-3 > 2,3-OBZ-1 > 2,3-OBZ-2 > 2,3-OBZ-3. The intracerebroventricular (i.c.v.) injection of aniracetam on it own (12.5-100 nmol/mouse) had no convulsant activity, but it reversed the anticonvulsant effects of some 2,3-benzodiazepines. In particular, the pharmacological actions of GYKI 52466, 2,3-BZ-2 and 2,3-BZ-2M, which proved to be the most potent 2,3-benzodiazepine derivatives as anticonvulsants, were significantly reduced by an i.c.v. pretreatment with aniracetam (50 nmol/mouse). Concomitant treatment with aniracetam (50 nmol/mouse) shifted to the right the dose-response curves and significantly increased the ED(50) values for GYKI 52466, 2,3-BZ-2 and 2,3-BZ-2M. After 30min pretreatment 2,3-BZ-2 showed a similar potency to GYKI 52466 in antagonizing seizures induced by i.c.v. administration of alpha-amino-3-hydroxy-methyl-4-isoxazolepropionic acid (AMPA), thus suggesting a clear involvement of AMPA receptors in the anticonvulsant activity of these compounds. In addition, 2,3-BZ-2 and 2,3-BZ-2M showed anticonvulsant properties longer lasting than GYKI 52466.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/03/20 alle ore 09:36:10