The pharmacological profile of amlodipine in relation to ischaemic heart disease.
Amlodipine is a novel dihydropyridine calcium antagonist with distinctive pharmacokinetic and pharmacodynamic properties, including slow onset and long duration of action, with minimal effects on cardiac electrophysiology and myocardial contractility. These unique pharmacokinetic and pharmacodynamic properties are believed to be related to the unusual physiochemical profile of amlodipine. Thus, despite being more polar than other dihydropyridines, due to the presence of a charged amino function, amlodipine shows exceptionally high affinity for biological membranes, possibly due to an electrostatic interaction with membrane phospholipid. This results in a large volume of distribution and hence a long elimination half-life. Results obtained from studies involving ischaemic/reperfused rat, cat and dog hearts showed that amlodipine had a protective effect on the ischaemic myocardium. Treatment with amlodipine was found to reduce myocardial oxygen demand, improve recovery of peak developed tension, have a favourable effect on Ca2+ fluxes, improve retention of tissue adenosine triphosphate and creatine phosphate, and reduce acidosis in the ischaemic/reperfused myocardium. Amlodipine therefore accelerated the recovery of both mechanical myocardial function and blood flow, producing a favourable effect on contractile and metabolic recovery, suggesting that amlodipine may have potential as a therapeutic agent in the treatment of ischaemic heart disease. The long duration of action associated with amlodipine may be of benefit in ischaemic heart disease, as an increase in myocardial ischaemia has been observed in the early hours when plasma levels are normally at their lowest.
Burges
R A
RA
Pfizer Central Research, Sandwich, Kent, UK.
D017311:Amlodipine; D000818:Animals; D002121:Calcium Channel Blockers / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D002415:Cats; D003327:Coronary Disease / Q000517:prevention & control*; D004285:Dogs; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats
D002121:Calcium Channel Blockers; D017311:Amlodipine; D009543:Nifedipine