Abstract
1. The electrophysiological effects of amoxapine were examined in guinea-pig isolated papillary muscles and rabbit sinoatrial nodes using a conventional microelectrode technique. 2. In papillary muscles, amoxapine above 10 microM caused a dose-dependent decrease in the maximum upstroke velocity (Vmax) of the action potential and in the action potential amplitude (APA), whereas the action potential duration at 90% repolarization (APD90) was significantly prolonged. For a decrease in Vmax, amoxapine produced a negative shift of the curve relating Vmax to the resting potential (Em) along the voltage axis to more negative membrane potentials. 3. Amoxapine also decreased Vmax and the overshoot potential of K+-depolarized slow action potentials of papillary muscle preparations. 4. In spontaneously beating sinoatrial node preparations, amoxapine above 3 microM reduced the heart rate, Vmax, APA and the slope of phase 4 depolarization in a dose-dependent manner. 5. It was concluded that amoxapine exerts inhibitory actions on fast- and slow-response fibres of the heart and these actions can be mainly explained by inhibition of both fast Na+ and slow Ca2+ channels.
Full text
PDF






Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Arita M., Kiyosue T., Aomine M., Imanishi S. Nature of "residual fast channel" dependent action potentials and slow conduction in guinea pig ventricular muscle and its modification by isoproterenol. Am J Cardiol. 1983 May 1;51(8):1433–1440. doi: 10.1016/0002-9149(83)90325-9. [DOI] [PubMed] [Google Scholar]
- Bock J. L., Cummings K. C., Jatlow P. I. Amoxapine overdose: a case report. Am J Psychiatry. 1982 Dec;139(12):1619–1620. doi: 10.1176/ajp.139.12.1619. [DOI] [PubMed] [Google Scholar]
- Bonke F. I. Electronic spread in the sinoatrial node of the rabbit heart. Pflugers Arch. 1973 Mar 5;339(1):17–23. doi: 10.1007/BF00586978. [DOI] [PubMed] [Google Scholar]
- Boutelle W. E. Clinical response and blood levels in the treatment of depression with a new antidepressant drug, amoxapine. Neuropharmacology. 1980 Dec;19(12):1229–1231. doi: 10.1016/0028-3908(80)90213-0. [DOI] [PubMed] [Google Scholar]
- Brennan F. J. Electrophysiologic effects of imipramine and doxepin on normal and depressed cardiac Purkinje fibers. Am J Cardiol. 1980 Oct;46(4):599–606. doi: 10.1016/0002-9149(80)90509-3. [DOI] [PubMed] [Google Scholar]
- De Jalon P. G., Rodriguez S. M., Tamargo J. Electrophysiological effects of imipramine in guinea pig-myocardium [proceedings]. Br J Pharmacol. 1978 Jun;63(2):373P–373P. [PMC free article] [PubMed] [Google Scholar]
- Delgado C., Manzanares J., Tamargo J., Valenzuela C. Electrophysiological effects of amoxapine in untreated and in amoxapine-pretreated rat atria. Br J Pharmacol. 1986 Feb;87(2):317–325. doi: 10.1111/j.1476-5381.1986.tb10820.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hisatome I., Kiyosue T., Imanishi S., Arita M. Isoproterenol inhibits residual fast channel via stimulation of beta-adrenoceptors in guinea-pig ventricular muscle. J Mol Cell Cardiol. 1985 Jul;17(7):657–665. doi: 10.1016/s0022-2828(85)80065-1. [DOI] [PubMed] [Google Scholar]
- Jue S. G., Dawson G. W., Brogden R. N. Amoxapine: a review of its pharmacology and efficacy in depressed states. Drugs. 1982 Jul;24(1):1–23. doi: 10.2165/00003495-198224010-00001. [DOI] [PubMed] [Google Scholar]
- Kotake H., Hasegawa J., Hata T., Mashiba H. Electrophysiological effect of disopyramide on rabbit sinus node cells. J Electrocardiol. 1985 Oct;18(4):377–383. doi: 10.1016/s0022-0736(85)80020-0. [DOI] [PubMed] [Google Scholar]
- Langslet A., Johansen W. G., Ryg M., Skomedal T., Oye I. Effects of dibenzepine and imipramine on the isolated rat heart. Eur J Pharmacol. 1971 May;14(4):333–339. doi: 10.1016/0014-2999(71)90186-5. [DOI] [PubMed] [Google Scholar]
- Lydiard R. B., Gelenberg A. J. Amoxapine--an antidepressant with some neuroleptic properties? A review of its chemistry, animal pharmacology and toxicology, human pharmacology, and clinical efficacy. Pharmacotherapy. 1981 Nov-Dec;1(3):163–178. doi: 10.1002/j.1875-9114.1981.tb02538.x. [DOI] [PubMed] [Google Scholar]
- Manzanares J., Tamargo J. Electrophysiological effects of imipramine in nontreated and in imipramine-pretreated rat atrial fibres. Br J Pharmacol. 1983 May;79(1):167–175. doi: 10.1111/j.1476-5381.1983.tb10509.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Marshall J. B., Forker A. D. Cardiovascular effects of tricyclic antidepressant drugs: therapeutic usage, overdose, and management of complications. Am Heart J. 1982 Mar;103(3):401–414. doi: 10.1016/0002-8703(82)90281-2. [DOI] [PubMed] [Google Scholar]
- Noma A., Irisawa H. Membrane currents in the rabbit sinoatrial node cell as studied by the double microelectrode method. Pflugers Arch. 1976 Jun 29;364(1):45–52. doi: 10.1007/BF01062910. [DOI] [PubMed] [Google Scholar]
- Rodriguez S., Tamargo J. Electrophysiological effects of imipramine on bovine ventricular muscle and Purkinje fibres. Br J Pharmacol. 1980 Sep;70(1):15–23. doi: 10.1111/j.1476-5381.1980.tb10899.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Seyama I. Characteristics of the rectifying properties of the sino-atrial node cell of the rabbit. J Physiol. 1976 Feb;255(2):379–397. doi: 10.1113/jphysiol.1976.sp011285. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Smith R. S., Jr, Ayd F. J., Jr A critical appraisal of amoxapine. J Clin Psychiatry. 1981 Jun;42(6):238–242. [PubMed] [Google Scholar]
- Tamargo J., Rodriguez S. Electrophysiological actions of chlorimipramine on guinea-pig ventricular fibres. Experientia. 1979 Mar 15;35(3):366–367. doi: 10.1007/BF01964356. [DOI] [PubMed] [Google Scholar]
- Tamargo J., Rodriguez S., Garcia de Jaloń P. Electrophysiological effects of desipramine on guinea pig papillary muscles. Eur J Pharmacol. 1979 Apr 15;55(2):171–179. doi: 10.1016/0014-2999(79)90389-3. [DOI] [PubMed] [Google Scholar]
- Taylor R. L., Crooks C. R., Caplan Y. H. The determination of amoxapine in human fatal overdoses. J Anal Toxicol. 1982 Nov-Dec;6(6):309–311. doi: 10.1093/jat/6.6.309. [DOI] [PubMed] [Google Scholar]
- Vohra J., Burrows G., Hunt D., Sloman G. The effect of toxic and therapeutic doses of tricyclic antidepressant drugs on intracardiac conduction. Eur J Cardiol. 1975 Oct;3(3):219–227. [PubMed] [Google Scholar]
- Windisch H., Tritthart H. A. Calcium ion effects on the rising phases of action potentials obtained from guinea-pig papillary muscles at different potassium concentrations. J Mol Cell Cardiol. 1981 May;13(5):457–469. doi: 10.1016/0022-2828(81)90263-7. [DOI] [PubMed] [Google Scholar]
