Interactions of amantadine with the cardiac muscarinic receptor.
The antiviral drug amantadine has anticholinergic effects in the guinea-pig atrium at concentrations greater than 1 X 10(-4)M. It is a competitive inhibitor of [3H]-quinuclidinyl benzilate binding to the muscarinic receptor, but antagonizes the negative inotropic effect of acetylcholine in a non-competitive manner. It increases the duration of the atrial action potential and also increases the force of atrial contraction. These effects are evident at approximately 10 times lower concentrations than the antimuscarinic effects. The increase in contractility can be reversed by propranolol (5 X 10(-7)M) but the increase in action potential duration is potentiated by propranolol. Shortening of the action potential duration by acetylcholine was reversed by amantadine, but at approximately ten times lower levels than were needed to reduce the negative inotropic effect. Interactions between beta adrenoceptor binding of [3H]-dihydroalprenolol and amantadine could not be demonstrated. Similarly, binding of [3H]-nitrendipine to the calcium channel is not influenced. It is suggested that amantadine may exert its positive inotropic effect by interaction with the potassium channel, causing a delay in outward current.
Freeman
S E
SE
Dawson
R M
RM
Culvenor
A J
AJ
Keeghan
A M
AM
D000109:Acetylcholine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000547:Amantadine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D004082:Dihydroalprenolol / Q000378:metabolism; D004562:Electrocardiography; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects* / Q000378:metabolism; D006329:Heart Conduction System / Q000187:drug effects*; D007473:Ion Channels / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D009543:Nifedipine / Q000031:analogs & derivatives / Q000378:metabolism; D009568:Nitrendipine; D011433:Propranolol / Q000494:pharmacology; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000378:metabolism
D007473:Ion Channels; D011976:Receptors, Muscarinic; D004082:Dihydroalprenolol; D011813:Quinuclidinyl Benzilate; D009568:Nitrendipine; D011433:Propranolol; D000547:Amantadine; D009543:Nifedipine; D000109:Acetylcholine