MOTOR-NERVE TERMINAL FACILITATORY ACTION OF SQ 20009 - INHIBITOR OF CYCLIC NUCLEOTIDE PHOSPHODIESTERASE

  • 1 January 1977
    • journal article
    • research article
    • Vol. 202  (2) , 404-410
Abstract
Facilitatory effects of SQ 20009 [1-ethyl-4-(isopropylidenehydrazino)-1H-pyrazolo-(3,4-b)-pyridine-5-carboxylic acid, ethyl ester, HCl] were investigated at the frog sartorious neuromuscular junction. A dose-dependent increase in miniature end-plate potential [MEPP] frequency occurred without changes in MEPP amplitude. Significant increases in the amplitude and the rate of rise of the EPP and reduction in the incidence of EPP failures were observed in Mg blocked muscle. The increase in EPP amplitude and rate of rise appeared C dependent. No significant changes in passive membrane resistance or muscle membrane sensitivity to acetylcholine were observed. Twitch studies employing direct and indirect stimulation of the rat diaphragm preparation demonstrated a preferential facilitation of the indirect response rather than a direct action on the muscle fiber. The facilitatory effect of SQ 20009 on evoked and spontaneous release were of approximately equal orders of magnitude, suggesting that the drug may affect a common mechanism in the 2 release processes.