Effects of a new analog of thyrotropin-releasing hormone, N alpha-[(S)-4-oxo-2-azetidinyl) carbonyl]-L-histidyl-L-prolinamide dehydrate (YM-14673) on spinal reflex potentials and flexor reflexes in spinalized rats.
Experiments were performed on spinalized rats, transected at the Cl level. The intravenous administration of TRH and its analog YM-14673 (N alpha-[(S)-4-oxo-2-azetidinyl) carbonyl]-L-histidyl-L-prolinamide dehydrate) produced marked increases in the amplitude of mono- and polysynaptic reflex potentials and those of the withdrawal flexor reflexes. The effects of YM-14673 were stronger and longer-lasting than those of TRH. The stimulant action of TRH and YM-14673 on the flexor reflexes was not antagonized by prazosin, chlorpromazine, haloperidol or cyproheptadine, suggesting no involvement of the release of catecholamines or serotonin in the stimulant effects of TRH and its analog. Therefore, YM-14673 may be beneficial for the treatment of several spinal motor neuron diseases.
Ono
H
H
Department of Toxicology and Pharmacology, Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
Nagano
N
N
Yamada
M
M
Fukuda
H
H
D000818:Animals; D001384:Azetidines / Q000494:pharmacology*; D001385:Azetines / Q000494:pharmacology*; D003655:Decerebrate State; D004151:Dipeptides / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012018:Reflex / Q000187:drug effects*; D012023:Reflex, Monosynaptic / Q000187:drug effects; D013116:Spinal Cord / Q000502:physiology*; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology
D001384:Azetidines; D001385:Azetines; D004151:Dipeptides; D013973:Thyrotropin-Releasing Hormone; C054995:azetirelin