Ion channel inhibitors may function as potential modulators of cocaine binding.
The effects of NaCl, KCl and Ca2Cl were determined in a binding assay, using the analog of cocaine [3H]WIN 35,428. The addition of NaCl had no effect upon specific binding; however, Ca2Cl and to a lesser extent, KCl decreased binding. Various Na+, K+, Cl- and Ca2+ channel antagonists were tested for their ability to inhibit specific binding of [3H]WIN 35,428. Most of the Na+ channel blockers tested were of moderate affinity, the exceptions being benzamil and flunarizine. Both of these agents also show activity at the Ca2+ channel. The K+ channel blockers were of low and moderate affinity, while the Cl- channel blockers had no effect. Of the Ca2+ channel blockers tested, only pimozide demonstrated a high affinity. This was postulated to be due to its ability to act upon both L and T-type channels. These results suggest that the Ca2+ channel blockers deserve further study as potential useful therapeutic agents in the treatment of cocaine addiction.
Boja
J W
JW
Neuroscience Branch, National Institute on Drug Abuse, Addiction Research Center, Baltimore, MD 21224.
Kopajtic
T A
TA
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003042:Cocaine / Q000031:analogs & derivatives / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects*; D008297:Male; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism
D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D007473:Ion Channels; D015221:Potassium Channels; D015222:Sodium Channels; C021279:(1R-(exo,exo))-3-(4-fluorophenyl)-8-methyl-8- azabicyclo(3.2.1)octane-2-carboxylic acid, methyl ester; D003042:Cocaine