Strychnine-like action of the convulsant barbiturate, CHEB.
The effect of 5-(2-cyclohexylideneethyl)-5-ethyl barbituric acid (CHEB) on the isolated spinal cord of the immature rat was examined using extracellular recording. At concentrations less than 20 microM CHEB increased the monosynaptic reflex (MSR) but depressed the reflex at greater concentrations (30-100 microM). At concentrations which enhanced the monosynaptic reflex, CHEB reduced the responses of motoneurones to glycine and to a lesser extent to those of L-glutamate. In the presence of strychnine (5 microM), which enhanced both mono- and polysynaptic reflexes, CHEB produced only slight enhancement of the monosynaptic reflex. At concentrations of 30-100 microM the responses to gamma-aminobutyric acid (GABA), glycine, L-glutamate and eledoisin-related peptide (ERP a substance P and analogue) were all reduced. At these concentrations CHEB directly depolarised the motoneurone membrane. Increases in [Mg2+]0, which reduced spontaneous activity, blocked the enhancement, by CHEB, of the monosynaptic reflex. The actions of CHEB in small doses may be due therefore to its ability to block the action of glycine and thus block tonic inhibition.
Nicholson
G M
GM
Spence
I
I
Johnston
G A
GA
D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D000927:Anticonvulsants / Q000494:pharmacology*; D001463:Barbiturates / Q000031:analogs & derivatives / Q000494:pharmacology*; D003292:Convulsants; D004347:Drug Interactions; D004600:Eledoisin / Q000494:pharmacology; D005260:Female; D008297:Male; D009046:Motor Neurons / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012023:Reflex, Monosynaptic / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects; D013331:Strychnine / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D000596:Amino Acids; D000927:Anticonvulsants; D001463:Barbiturates; D003292:Convulsants; C024321:5-(2-cyclohexylidene-ethyl)-5-ethylbarbiturate; D005680:gamma-Aminobutyric Acid; D004600:Eledoisin; D013331:Strychnine