Inhibitory effects of some cyclohexylaralkylamines related to perhexiline on sodium influx, binding of [3H]batrachotoxinin A 20-alpha-benzoate and [3H]nitrendipine and on guinea pig left atria contractions.
The antagonist activities of some cyclohexylaralkylamines derived from perhexiline on the fast Na+ channel and slow Ca2+ channel in rat brain and rat heart were examined and compared to the antagonist activities of nifedipine, verapamil, prenylamine and perhexiline. Prenylamine, perhexiline and the cyclohexylaralkylamine derivatives inhibited the [3H]batrachotoxinin A 20-alpha-benzoate binding more than the [3H]nitrendipine binding in rat brain. The nature of the interaction of the cyclohexylaralkylamines with the binding of [3H]batrachotoxinin and [3H]nitrendipine was non-competitive. The synaptosomal 22Na uptake induced by protoveratrine B, a Na+ channel agonist, was also inhibited. Prenylamine, perhexiline and perhexiline derivatives were more potent on the fast Na+ channel than on the Ca2+ channel in contrast to nifedipine and verapamil. The inhibition of Na+ and Ca2+ channels was also shown in guinea pig left atria. Perhexiline, prenylamine and the perhexiline derivatives inhibited the protoveratrine B-induced contraction more than they inhibited that induced by CaCl2, in contrast with nifedipine and verapamil. Our results showed that prenylamine, perhexiline and its related cyclohexylaralkylamines inhibited the fast Na+ channel far more than the slow Ca2+ channel in rat brain, rat heart and guinea pig atria.
Grima
M
M
Laboratoire de Pharmacologie Cardiovasculaire et Rénale, UA 589 CNRS, Faculté de Médecine, Strasbourg, France.
Velly
J
J
Decker
N
N
Marciniak
G
G
Schwartz
J
J
D000818:Animals; D001496:Batrachotoxins / Q000378:metabolism*; D001667:Binding, Competitive / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000378:metabolism*; D002122:Calcium Chloride / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009568:Nitrendipine / Q000378:metabolism*; D010480:Perhexiline / Q000031:analogs & derivatives* / Q000494:pharmacology*; D011526:Protoveratrines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism*; D012979:Sodium Radioisotopes; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D001496:Batrachotoxins; D002121:Calcium Channel Blockers; D011526:Protoveratrines; D012979:Sodium Radioisotopes; C031775:batrachotoxinin A 20-alpha-benzoate; D009568:Nitrendipine; D012964:Sodium; D010480:Perhexiline; D002122:Calcium Chloride