MDL 27,531 reduces spontaneous hindlimb contractions in rats with chronic transections of the spinal cord.
Disrupted glycinergic inhibition in the brainstem and spinal cord may contribute to some of the alterations in reflex control seen in patients with spastic disorders. MDL 27,531, which acts functionally like a glycine agonist in its capacity to selectively reverse seizures produced by the glycine antagonist strychnine, was evaluated in a model of spinal injury-induced reflex dysfunction. Rats recovering chronically from complete spinal cord transections exhibited intermittent contractions of the paralyzed hindlimbs, as measured with an automated apparatus. MDL 27,531 selectively decreased these hindlimb contractions, as did the clinically demonstrated antispastic agent clonidine. In its therapeutic dose range, clonidine, but not MDL 27,531, produced ataxia in non-transected rats. These data suggest that MDL 27,531 may be a useful therapeutic agent for the treatment of dysfunctions of reflex control seen in spastic disorders of spinal origin, with potentially fewer side effects than are seen with existing drug therapies.
Kehne
J H
JH
Marion Merrell Dow Research Institute, Cincinnati, OH 45215.
Ketteler
H J
HJ
Kane
J M
JM
McCloskey
T C
TC
Senyah
Y
Y
Palfreyman
M G
MG
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D003000:Clonidine / Q000494:pharmacology; D003655:Decerebrate State; D006614:Hindlimb / Q000502:physiology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009129:Muscle Tonus / Q000187:drug effects; D004856:Postural Balance / Q000187:drug effects / Q000502:physiology; D051381:Rats; D014230:Triazoles / Q000494:pharmacology*
D000927:Anticonvulsants; D014230:Triazoles; C077362:4-methyl-3-methylsulfonyl-5-phenyl-4H-1,2,4-triazole; D003000:Clonidine