Occupancy by oral administration of nicardipine of L-type calcium channels in rat brain.
The occupancy of L-type Ca2+ channels by treatment with an oral dose of the dihydropyridine-type Ca2+ antagonist nicardipine (sustained-release formulation) was evaluated in membrane preparations of rat frontal cortex and hippocampus using a radioligand binding assay technique, with [3H]-nicardipine as a ligand. Three hours after nicardipine administration, specific binding was decreased by about 15-20%, both in the frontal cortex and hippocampus. This indicates that oral nicardipine occupied approximately 15-20% of L-type Ca2+ channels. A progressive occupancy of Ca2+ channels was observed between six and 12 h after nicardipine administration. Twelve hours after drug administration, approximately 65-70% of Ca2+ channels were occupied. These findings indicate that oral treatment with 3 mg/kg of nicardipine (sustained-release formulation) occupies L-type Ca2+ channels in rat brain by more than 40% from the 6th to the 24th h after drug administration. This suggests that an oral dose of nicardipine (sustained-release formulation) in duces a significant occupancy of L-type Ca2+ channels in rat frontal cortex and hippocampus for about one day. The possible clinico-therapeutic relevance of this observation is discussed.
Dipartimento di Scienze Farmacologiche e Medicina Sperimantale, Università di Camerino, Italy. amenta@cambio.unicam.it
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D000284:Administration, Oral; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000008:administration & dosage* / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D003692:Delayed-Action Preparations; D006624:Hippocampus / Q000378:metabolism; D007700:Kinetics; D008297:Male; D009529:Nicardipine / Q000008:administration & dosage* / Q000378:metabolism*; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D003692:Delayed-Action Preparations; D009529:Nicardipine