Differing actions of convulsant and nonconvulsant barbiturates: an electrophysiological study in the isolated spinal cord of the rat.
The effects of various pairs of convulsant and nonconvulsant barbiturates on mono- and polysynaptic activity were studied in the isolated spinal cord of the immature rat, using extracellular recording. The convulsant barbiturates, 5-ethyl-5-(3-methylbut-2'-enyl) barbituric acid (3M2B), 5-ethyl-5-(1,3-dimethylbut-1'-enyl) barbituric acid (1,3M1B) and (+)-5-(1,3-dimethylbutyl)-5-ethyl barbituric acid [(+) DMBB] all increased the monosynaptic reflex at concentrations between 5 and 50 microM with no change in polysynaptic activity. When the concentration was raised to between 100 and 300 microM, however, the convulsants all reduced the monosynaptic reflex, thus producing a biphasic dose-response relationship. The nonconvulsant barbiturates phenobarbital, 5-ethyl-5-(3-methylbut-1'-enyl) barbituric acid (3M1B), amylobarbital (3MB) and (-)-5-(1,3-dimethylbutyl)-5-ethyl barbituric acid [(-)DMBB] produced only a decrease in mono- and polysynaptic reflexes. At concentrations which enhanced the monosynaptic reflex, the responses of motoneurones to glycine and eledoisin-related peptide (an analogue of substance P) were reduced by (+)DMBB, while 1,3M1B and 3M2B had no significant effects upon any of the neurotransmitters tested. At concentrations which depressed the monosynaptic reflex, the convulsants all reduced the response to glycine whereas the nonconvulsant barbiturates all increased the response to GABA. With the exception of phenobarbital, both convulsant and nonconvulsant barbiturates produced a direct depolarisation of the presynaptic terminal membrane, with only the convulsants producing a depolarisation of the membrane of the motoneurone. Using another convulsant barbiturate, 5-(2-cyclohexylideneethyl)-5-ethyl barbituric acid (CHEB), this direct depolarising action was found to be calcium-dependent.
Nicholson
G M
GM
Department of Applied Biology, N.S.W. Institute of Technology, Sydney, Australia.
Spence
I
I
Johnston
G A
GA
D000818:Animals; D001463:Barbiturates / Q000494:pharmacology*; D003292:Convulsants / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D004600:Eledoisin / Q000494:pharmacology; D005260:Female; D005727:Ganglia, Spinal / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009046:Motor Neurons / Q000187:drug effects; D009475:Neurons, Afferent / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012023:Reflex, Monosynaptic / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology
D001463:Barbiturates; D003292:Convulsants; D013779:Tetrodotoxin; D004600:Eledoisin