[Antagonism of the novel cholinolytic tricyclopinate on nicotinic and muscarinic cholinergic receptors].
Tricyclopinate hydrochloride(TCPN.HCl) and methiodide(TCPN.CH3I) have been identified as new chemical entities. The effects of these two compounds on central and peripheral nicotinic and muscarinic cholinergic receptor activities were investigated. Excitation of the central nicotinic receptors by nicotine produced convulsions in mice. The dose-response curves of nicotine for producing convulsions were shifted rightward by TCPN.CH3I in a paralled manner. Excitation of the central muscarinic receptors by arecoline produced tremors in mice. TCPN.HCl was shown to prevent arecoline-induced tremors. In isolated guinea-pig ileum preparations. TCPN.HCl was found to antagonize nicotine-induced contractions due to excitation of ganglionic nicotinic receptors. In xenopus laevis embryo neuron-muscle co-cultured cells, TCPN.HCl blocked spontaneous miniature endplate currents, and showed preference to blocking the nicotinic receptor ion channels, which had a long open time, and high current amplitude. The anticholinergic effects of TCPN.CH3I were weaker than those of TCPN.HCl. In conclusion, TCPN.HCl has potent effects against nicotinic and muscarinic receptors in the central and periphery nervous systems.
Wang
H
H
Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing 100850.
Cui
W
W
Xie
Z
Z
Liu
C
C
D000818:Animals; D004622:Embryo, Mammalian; D004625:Embryo, Nonmammalian; D005260:Female; D006168:Guinea Pigs; D006575:Heterocyclic Compounds, 3-Ring / Q000494:pharmacology*; D007082:Ileum / Q000187:drug effects; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D011976:Receptors, Muscarinic / Q000187:drug effects*; D011978:Receptors, Nicotinic / Q000187:drug effects*; D012640:Seizures / Q000517:prevention & control; D014982:Xenopus laevis
D006575:Heterocyclic Compounds, 3-Ring; D011976:Receptors, Muscarinic; D011978:Receptors, Nicotinic; C437004:tricyclopinate