Anticonvulsant effects of carbenoxolone in genetically epilepsy prone rats (GEPRs).
Carbenoxolone (CBX), the succinyl ester of glycyrrhetinic acid, is an inhibitor of gap junctional intercellular communication. Systemic administration of CBX was able to decrease the seizure severity score and to increase the latency time of seizure onset in genetically epilepsy prone rats (GEPRs). In particular, intravenous or intraperitoneal administration of carbenoxolone (5-30 mg/kg) produced a dose-dependent and significant reduction in the clonic and tonic phases of the audiogenic seizures in GEPRs. The anticonvulsant doses were not associated with an impairment of motor coordination. The bilateral microinjection of CBX (0.001-0.50 microg/0.5 microl) into the inferior colliculi, the substantia nigra (pars reticulata or compacta) and the inferior olivary complex was able to reduce the seizure severity score in a dose-dependent manner. The anticonvulsant effects were longer lasting after focal microinjection than after systemic administration. No anticonvulsant effects were observed following focal bilateral microinjections of glycyrrhizin into the same brain areas where CBX was shown to be effective.
Gareri
Pietro
P
Section of Pharmacology, Department of Experimental and Clinical Medicine, Faculty of Medicine and Surgery, University of Catanzaro, 88100 Catanzaro, Italy.
Condorelli
Daniele
D
Belluardo
Natale
N
Russo
Emilio
E
Loiacono
Antonella
A
Barresi
Vincenza
V
Trovato-Salinaro
Angela
A
Trovato-Salinato
Angela
A
Mirone
Melita B
MB
Ferreri Ibbadu
Guido
G
De Sarro
Giovambattista
G
D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D002229:Carbenoxolone / Q000627:therapeutic use*; D017630:Connexins / Q000096:biosynthesis; D004827:Epilepsy / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D005260:Female; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D000097004:Gap Junction delta-2 Protein
D000927:Anticonvulsants; D002229:Carbenoxolone; D017630:Connexins; D000097004:Gap Junction delta-2 Protein