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  • Title: Analogs of thyrotropin-releasing hormone in potentiating the spinal monosynaptic reflex in vitro.
    Author: Deshpande SB, Warnick JE.
    Journal: Eur J Pharmacol; 1994 Dec 27; 271(2-3):439-44. PubMed ID: 7705444.
    Abstract:
    The efficacy of thyrotropin-releasing hormone (TRH) and its analogs to potentiate the spinal monosynaptic reflex was studied in isolated cords. The analogs examined were L-pyro-2-aminoadipyl-histidyl-thizolidine-4-carboxyamide (MK-771); pyroglutamyl-histidyl-prolineamide (TRH); pyroglutamyl-L-histidyl-3,3'-dimethyl-prolineamide (RX77368); (3-methyl-His2)TRH(methyl-TRH); gamma-buturolactone-gamma-carbonyl-histidyl-prolineamide citrate (DN-1417); pyroglutamyl-histidyl-proline (TRH-free acid); and histidyl-proline-diketopiperazine (cyclo(His-Pro)). The TRH analogs potentiated the monosynaptic reflex in a dose-dependent manner and the maximal potentiation occurred at about 1 microM. TRH-free acid potentiated the monosynaptic reflex but the maximal potentiation occurred at 100 times the TRH concentration. Cyclo(His-Pro) was totally ineffective. The concentration required to potentiate the monosynaptic reflex by 50% of the maximal response (EC50) was taken as an index for comparing various analogs in relation to TRH. The EC50 values of the analogs did not differ significantly from each other. However, the ratio of the mean value of an analog to that of TRH was of the following order: MK-771 (N- and C-terminally altered) > or = TRH > or = DN-1417 (N-terminal) > or = methyl-TRH > or = RX77368 (C-terminal) >>> TRH-free acid. Cyclo(His-Pro) was ineffective.
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