Hybridized and isosteric analogs of N1-acetyl-N4-dimethyl-piperazinium iodide (ADMP) and N1-phenyl-N4-dimethyl-piperazinium iodide (DMPP) with central nicotinic action

A series of piperazine derivatives, obtained by hybridization of N1-acetyl-N4-dimethyl-piperazinium iodide (1, ADMP) and N1-phenyl-N4-dimethyl-piperazinium iodide (3, DMPP) or of the corresponding tertiary bases (2, 4) with arecoline (5) and arecolone (6) or by isosteric substitution of the phenyl ring of DMPP, has been synthesized. Hybridization a orded compounds that, both as tertiary bases and as iodomethylates, have no a nity for the nicotinic receptor. On the contrary, isosteric substitution gave compounds that maintain a nity for the receptor; among them, two tertiary bases (37, 38), show a nity in the nanomolar range for the nicotinic receptor. The pharmacological pro®le of these isomeric compounds is quite interesting as they present dif- ferences in their peripheral and central e ects, suggesting that they interact with di erent subtypes of the nicotinic receptor.