Binding characteristics of a new 1,5-benzothiazepine, clentiazem, to rat cerebral cortex and skeletal muscle membranes.
The binding properties of a new 1,5-benzothiazepine, clentiazem (TA-3090), were investigated in rat cerebral cortex and skeletal muscle membranes with [3H]diltiazem and [3H]nitrendipine as radioligands. Clentiazem inhibited [3H]diltiazem binding to cerebral cortex membranes at the same concentrations as diltiazem at 2 degrees C. However, at 37 degrees C clentiazem was 3 times more potent to inhibit binding than diltiazem. [3H]Nitrendipine binding was modulated by clentiazem in a temperature-dependent manner. At 37 degrees C clentiazem significantly enhanced [3H]nitrendipine binding to rat cerebral cortex membranes, whereas it has an inhibitory effect on [3H]nitrendipine binding at 0 degree C and no effect at 25 degrees C. Of two optical isomers of clentiazem and four of diltiazem, only d-cis isomers (clentiazem and diltiazem) increased [3H]nitrendipine binding, indicating that both compounds have the same stereoselectivity for increasing [3H]nitrendipine binding. These results suggest that clentiazem binds to the same 1,5-benzothiazepine binding sites as diltiazem but with greater affinity.
Suzuki
T
T
Biological Research Laboratory, Tanabe Seiyaku Co., Ltd., Saitama, Japan.
Kurosawa
H
H
Naito
K
K
Otsuka
M
M
Ohashi
M
M
Takaiti
O
O
D000818:Animals; D001665:Binding Sites; D002121:Calcium Channel Blockers / Q000378:metabolism* / Q000494:pharmacology; D002540:Cerebral Cortex / Q000378:metabolism* / Q000648:ultrastructure; D004110:Diltiazem / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D008566:Membranes / Q000378:metabolism; D009132:Muscles / Q000378:metabolism*; D009568:Nitrendipine / Q000378:metabolism / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism; D014316:Tritium
D002121:Calcium Channel Blockers; D014316:Tritium; C056595:clentiazem; D009568:Nitrendipine; D004110:Diltiazem