Slow association of positively charged Ca2+ channel antagonist amlodipine to dihydropyridine receptor sites in rat brain membranes.
1. No significant differences were observed in Kd and Bmax values between pH 7.2 (0.16 +/- 0.01 nM and 155.36 +/- 16.07 fmol/mg protein) and pH 10.0 (0.15 +/- 0.01 nM and 158.63 +/- 13.80 fmol/mg protein) in rat brain membranes. 2. The IC50 ratios at 0- and 270-min preincubations of amlodipine and manidipine at pH 7.2 were 23.09 and 10.25, respectively, whereas these ratios for these two drugs at pH 10.0 were 2.63 and 1.34, respectively. 3. In contrast, on treatment with nisoldipine, benidipine, SM-6586 and nifedipine, no significant differences were observed in the IC50 ratios between 0- and 270-min preincubations at pH 7.2 and 10.0.
Qu
Y L
YL
Department of Pharmacology, Niigata College of Pharmacy, Japan.
Sugiyama
K
K
Hattori
K
K
Yamamoto
A
A
Watanabe
K
K
Nagatomo
T
T
D017311:Amlodipine / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D020746:Calcium Channels, L-Type; D006863:Hydrogen-Ion Concentration; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D009419:Nerve Tissue Proteins; D017311:Amlodipine