20 November 2017

Coniine - a piperidine alkaloid

Natural toxin

Piperidine alkaloids are natural compounds isolable from Apiaceae family (e.g Conium maculatum). Coniine is a nicotinic antagonist, which disrupts the function of central nervous system.

Piperidine alkaloids are organic compounds containing saturated heterocyclic amine ring, i.e piperidine nucleus – a six membered ring consists of five methylene bridge (-CH2-) and one amine (-NH2-) bridge. Coniine (2-propylpiperidine, C8H17N) is one of the most known and abundant poisons piperidine alkaloid extractable from Apiaceae (Carrot) family. Thus, it accounts for the most of the plants acute and chronic toxicity.

Naturally coniine exists in two optically active forms, (+)- and (−)-coniine enantiomers, with (+)-coniine as the predominant enantiomer. However, (−)-coniine enantiomer is biologically more active than the (+)-coniine enantiomer. The structure, size of side chain attached to the ring, plays a significant role in the specific toxicity of the piperidine alkaloids. For instance, 2-ethylpiperidine showed no teratogenic activity whereas 2-propylpiperidine did.

Structure of coniine. Click image for 3D structure

Coniine is a neurotoxin, which leads to inhibition of the nervous system, and is toxic to human and all livestock. It exerts inhibitory effects on nicotinic receptor-mediated nitrergic and noradrenergic transmitter response. The symptom includes loss of sensation, weakness and drowsiness, paresthesia, ataxia and bradycardia followed by tachycardia.

SMILES: CCC[C@H]1CCCCN1

Pubchem CID: 441072

References:  

  • Hotti H & Rischer H (2017). The killer of Socrates: Coniine and related alkaloids in the plant kingdom: Review. Molecules, 22: 1962.  
  • Lee ST, Green B T, Welch KD, Pfister JA, & Panter KE (2008). Stereoselective potencies and relative toxicities of coniine enantiomers. Chem. Res. Toxicol, 21: 2061–2064. 
  • Erkent U, Iskit A, Onur R & Ilhan M (2016). The effect of coniine on presynaptic nicotinic receptors. Zeitschrift für Naturforschung C, 71(5-6): 115-120.     
  • Lopez TA, Cid MS, & Bianchini ML (1999). Biochemistry of hemlock (Conium maculatum L.) alkaloids and their acute and chronic toxicity in livestock: A review. Toxicon, 37:841-865.