The effect of coniine on presynaptic nicotinic receptors

Abstract

Toxicity of coniine, an alkaloid of Conium maculatum (poison hemlock), is manifested by characteristic nicotinic clinical signs including excitement, depression, hypermetria, seizures, opisthotonos via postsynaptic nicotinic receptors. There is limited knowledge about the role of presynaptic nicotinic receptors on the pharmacological and toxicological effects of coniine in the literature. The present study was undertaken to evaluate the possible role of presynaptic nicotinic receptors on the pharmacological and toxicological effects of coniine. For this purpose, the rat anococcygeus muscle and guinea-pig atria were used in vitro. Nicotine (100 μM) elicited a biphasic response composed of a relaxation followed by contraction through the activation of nitrergic and noradrenergic nerve terminals in the phenylephrine-contracted rat anococcygeus muscle. Coniine inhibited both the nitrergic and noradrenergic response in the muscle (-logIC(50) = 3.79 ± 0.11 and -logIC(50) = 4.57 ± 0.12 M, respectively). The effect of coniine on nicotinic receptor-mediated noradrenergic transmission was also evaluated in the guinea-pig atrium (-logIC(50) = 4.47 ± 0.12 M) and did not differ from the -logIC(50) value obtained in the rat anococcygeus muscle. This study demonstrated that coniine exerts inhibitory effects on nicotinic receptor-mediated nitrergic and noradrenergic transmitter response.

Secondary Metabolites with Biomedical Applications from Plants of the Sarraceniaceae Family

“…Coniine has significant effects on presynaptic nicotinic acetylcholine receptors. These could make it useful as a presynaptic nicotinic receptor antagonist in pharmacological studies [ 267 ]. It could be employed particularly for pain relief without an addictive side effect [ 268 ].…”

The killer of Socrates: Coniine and Related Alkaloids in the Plant Kingdom

“…Coniine, γ-coniceine and N -methylconiine block or reduce the response of muscle to acetylcholine [ 109 ] due to alkaloid binding to the nicotinic receptor of neuromuscular cells [ 114 , 116 ]. Coniine also exerts inhibitory effects on nicotinic receptor-mediated nitrergic and noradrenergic transmitter response in rat anococcygeus muscle via the inhibition of presynaptic nAChR [ 117 ]. When compared to different alkaloids in nAChR of fetal rat muscle, the efficiency is, from the highest to the lowest: nicotine > coniine > tubocurarine > lobeline [ 118 ].…”