Z-338, a newly synthetized carboxyamide derivative, stimulates gastric motility through enhancing the excitatory neurotransmission

J Smooth Muscle Res. 2000 Apr;36(2):69-81. doi: 10.1540/jsmr.36.69.


We studied the effects of Z-338, a newly synthesized carboxyamide derivative, on autonomic neuroeffector transmission in the guinea-pig stomach in relation to its gastrointestinal prokinetic action, by use of tension recording and microelectrode methods. Z-338 (>10(-8) M) dose-dependently enhanced the amplitude of twitch-like contractions and excitatory junction potentials (EJPs) evoked by single or repetitive electrical field stimulation (EFS) without affecting the non-adrenergic non-cholinergic (NANC) relaxation and inhibitory junction potentials (IJPs) in the circular muscle strips of the guinea-pig stomach. Similar to the action of Z 338, pirenzepine (> 10(-8) M), a muscarinic M1-antagonist, enhanced the EJP amplitude, although AF-DX116 (M2-) and 4-DAMP (M3-antagonists) reduced the EJP amplitude, dose-dependently. The EC50 of the Z-338 and pirenzepine concentration response curves on EJPs were 4.7 x 10(-8) M and 1.0 x 10(-8) M, and Hill coefficients were 0.96 and 0.94 respectively. In addition, Z-338 slightly but significantly enhanced the amplitude of slow waves with or without initial spike. These results provide the first evidence that Z-338 exerts its gastrointestinal prokinetic action mainly through enhancing excitatory neuro effector transmission with no effect on NANC inhibitory neuro-effector transmission in the guinea-pig stomach.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzamides / pharmacology*
  • Gastrointestinal Agents / pharmacology*
  • Gastrointestinal Motility / drug effects*
  • Gastrointestinal Motility / physiology*
  • Guinea Pigs
  • Male
  • Muscle Contraction / drug effects
  • Muscle, Smooth / drug effects
  • Muscle, Smooth / physiology
  • Stomach / innervation
  • Stomach / physiology*
  • Thiazoles / pharmacology*


  • Benzamides
  • Gastrointestinal Agents
  • Thiazoles
  • Z 338