Synthesis and pharmacology of alkanediguanidinium compounds that block the neuronal nicotinic acetylcholine receptor.
Taking as models the polyamine toxin fraction FTX from the funnel-web spider venom, and the guanidinium moiety of guanethidine, a series of azaalkane-1, omega-diguanidinium salts were obtained. Some of them blocked ion fluxes through the neuronal nicotinic receptors for acetylcholine (nAChR). The blockade was exerted at submicromolar concentrations, suggesting a highly selective interaction with the nAChR. In fact, the active compounds on the nAChR ion channel did not recognize the voltage-dependent Na+ or Ca2+ channels of bovine adrenal chromaffin cells. Therefore, these compounds may be useful tools to clarify the functions of nAChR receptors in the central and peripheral nervous systems.
Villarroya
M
M
Departamento de Farmacología, Facultad de Medicina, Universidad Autónoma de Madrid, Spain.
Gandía
L
L
López
M G
MG
García
A G
AG
Cueto
S
S
García-Navio
J L
JL
Alvarez-Builla
J
J
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers; D002417:Cattle; D019439:Chromaffin Cells / Q000187:drug effects / Q000378:metabolism; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology; D004594:Electrophysiology; D006145:Guanethidine / Q000031:analogs & derivatives* / Q000737:chemistry; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018733:Nicotinic Antagonists / Q000138:chemical synthesis*; D011073:Polyamines / Q000737:chemistry*; D011188:Potassium / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism*; D013111:Spider Venoms / Q000737:chemistry*
D002121:Calcium Channel Blockers; C071920:FTX, spider toxin; D018733:Nicotinic Antagonists; D011073:Polyamines; D011978:Receptors, Nicotinic; D013111:Spider Venoms; D004246:Dimethylphenylpiperazinium Iodide; D011188:Potassium; D002118:Calcium; D006145:Guanethidine