[A TRH analog (DN-1417). Anti-reserpine action in electroconvulsive threshold and involvement of serotonergic (5-HT) mechanism in mice].
The antagonistic effect of a TRH (Thyrotropin-releasing hormone) analog, DN-1417 (gamma-butyrolactone-gamma-carbonyl-L-histidyl-L-prolinamide citrate) against reserpine-induced reduction of electroconvulsive threshold (EC50) and the involvement of monoaminergic mechanism were studied in mice. Reserpine (2 mg/kg, i.p.) reduced the EC50 to 55-77% of the control in association with the depletion of brain monoamine. TRH and DN-1417 significantly reversed the EC50 reduced by reserpine. DN-1417 partially recovered 5-HT level and increased in the brain levels of 3-methoxy-4-hydroxyphenylglycol, homovanillic acid and 5-hydroxyindoleacetic acid in reserpinized mice. Monoaminergic receptor blockers attenuated, but muscarinic blockers accelerated the antagonistic effects of DN-1417 on the EC50. Neither alpha-methyl-p-tyrosine nor FLA-63 inhibited the effects of DN-1417, whereas p-chlorophenylalanine not only inhibited the antagonistic effect of DN-1417 on the EC50 but also prevented the stimulation effect on 5-HT turnover. Therefore, the antagonistic effect of DN-1417 against reserpine on the EC50 is most likely mediated by the stimulation of monoamine turnover, especially 5-HT in mice.
D006916:5-Hydroxytryptophan / Q000627:therapeutic use; D000818:Animals; D000927:Anticonvulsants; D001679:Biogenic Amines / Q000032:analysis*; D001923:Brain Chemistry / Q000187:drug effects*; D004347:Drug Interactions; D004597:Electroshock; D007980:Levodopa / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D012110:Reserpine / Q000037:antagonists & inhibitors*; D012640:Seizures / Q000517:prevention & control*; D012701:Serotonin / Q000378:metabolism; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000627:therapeutic use
D000927:Anticonvulsants; D001679:Biogenic Amines; D012701:Serotonin; D007980:Levodopa; D013973:Thyrotropin-Releasing Hormone; D012110:Reserpine; C029762:DN 1417; D006916:5-Hydroxytryptophan