A study of the possible mechanisms underlying the convulsant actions of a linear expanded xanthine.
The actions of a mixture of the 4- and 9-chloro derivatives of the linear expanded xanthine 5,7-diethyl-2-chloroimidazo[4,5-g]quinazoline-6,8 (5H,7H)-dione (chloro-DCQD) on the isolated olfactory cortex slice of the rat have been investigated. Chloro-DCQD evoked a slowly-developing depolarization which intensified over a drug application period of at least 4 min. A pharmacological investigation of the response showed that it was not mediated by blockade of potassium channels or activation of voltage-gated sodium channels, by a stimulant action at receptors to gamma-aminobutyric acid (GABA), excitatory amino acids or acetylcholine, or by antagonism of adenosine receptors. Chloro-DCQD (2.5 mM) potentiated responses evoked by N-methyl-D-aspartate (NMDA), L-aspartate and L-glutamate, probably by overcoming the magnesium ion block of the ion channel of the NMDA receptor complex. Chloro-DCQD (2.5 or 5 mM) also increased pyramidal cell excitability and abolished GABA-mediated postsynaptic inhibition but did not affect the excitability of, or neurotransmitter release from, the terminals of the lateral olfactory tract. Chloro-DCQD competitively antagonized the inhibitory actions of adenosine on the olfactory cortex. These effects are consistent with the reported convulsant actions of chloro-DCQD.
Collins
G G
GG
University Department of Pharmacology and Therapeutics, Royal Hallamshire Hospital, Sheffield, U.K.
Anson
J
J
D000818:Animals; D001224:Aspartic Acid / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects; D003292:Convulsants; D005071:Evoked Potentials / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D016202:N-Methylaspartate; D009830:Olfactory Bulb / Q000187:drug effects; D011712:Pyramidal Tracts / Q000166:cytology / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013569:Synapses / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects; D014970:Xanthines / Q000633:toxicity*
D003292:Convulsants; D014970:Xanthines; D001224:Aspartic Acid; D016202:N-Methylaspartate