Design, synthesis and preliminary pharmacological evaluation of rigid analogues of the nicotinic agonist 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP)

Luca Guandalini,Elisabetta Martini,Fulvio Gualtieri,Katia Varani,M Novella Romanelli

doi:10.3998/ark.5550190.0005.525

Abstract

Some frozen analogues of 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP) and of 1-(3- pyridyl)piperazine have been synthesized and tested on rat cerebral cortex by means of binding studies. Among the synthesized substances, only compound 2c was found to displace ( 3 H)- cytisine from the nicotinic binding sites on rat cerebral cortex. Some possible explanations for the inactivity of the other compounds are given.

Highlights

Nicotinic acetylcholine receptors are ligand-gated ion channels which modulate synaptic transmission
17 different subunits have been identified in vertebrate species, and according to the subunit composition, location, and sensitivity to αbungarotoxin, they can be classified into different groups: 1) muscle-type receptors, found at the skeletal neuromuscular junction and in the electric organs of Torpedo fishes, formed by four different subunits (α1, β1, γ, δ or α1, β1, ε, δ); 2 αBTX-insensitive neuronal receptors, found in the peripheral and central nervous systems, formed by different combinations of α 2-6 and β 2-4 subunits; 3) α BTX-sensitive neuronal receptors, found in the CNS, containing α7-10 subunits
As a part of our research in the field of nicotinic ligands, we have recently reported the synthesis and pharmacological evaluation of a series of analogues of 1,1-dimethyl-4phenylpiperazinium iodide (DMPP)[22,23], dimethyl-4-phenylpiperazinium iodide (DMPP) N

Summary

Introduction

Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels which modulate synaptic transmission. Drying (Na2SO4) and removal of the solvent gave 1 of .41 g the title compound (white solid, 97% yield). The catalyst was filtered off and the solvent removed to give a residue that was purified by column chromatography (CHCl3/petroleum ether/Et2O/EtOH/NH3 360/900/360/180/9.9) obtaining 0.01 g of 2a and 0.01 g of 2b (9% yield).

Results

Conclusion