Anti-muscarinic actions of mitoxantrone in isolated heart muscles of guinea pigs.
A hypotheses that mitoxantrone is a competitive antagonist at muscarinic cholinergic receptors was examined in guinea-pig hearts. In isolated left atrial muscle preparations, electrically paced at 2 Hz, the muscarinic agonist, carbachol, caused a concentration-dependent decrease in developed tension. Mitoxantrone caused a parallel right-ward shift of the concentration-response curve for carbachol. Schild plots for the effect of mitoxantrone on the carbachol concentration-response relationship were linear with a slope of 0.88 which was not significantly different from the unity. The right-ward shift of the carbachol concentration-response relationship by mitoxantrone significantly reversed after an additional incubation with a mitoxantrone-free solution, although the reversal was incomplete after a 2-h incubation in the mitoxantrone-free solution. Mitoxantrone caused a concentration-dependent displacement of specific [3H]quinuclidinyl benzilate binding to membrane preparations obtained from ventricular muscles of guinea-pig hearts. These results indicate that mitoxantrone acts as a competitive antagonist for the muscarinic receptors.
Chugun
A
A
Department of Veterinary Pharmacology, School of Veterinary Medicine and Animal Sciences, Kitasato University, 35-1, Higashi 23-bancho, Aomori 034-8628, Towada, Japan.
Uchide
T
T
Fujimori
Y
Y
Temma
K
K
Hara
Y
Y
Sasaki
T
T
Akera
T
T
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D018679:Cholinergic Agonists / Q000494:pharmacology*; D003864:Depression, Chemical; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008942:Mitoxantrone / Q000494:pharmacology*; D018727:Muscarinic Antagonists / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects* / Q000502:physiology; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology; D013268:Stimulation, Chemical
D000700:Analgesics; D018679:Cholinergic Agonists; D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; D011813:Quinuclidinyl Benzilate; D002217:Carbachol; D008942:Mitoxantrone