Summary
The effects of mianserin, a tetracyclic antidepressant, and adinazolam, a new triazolobenzodiazepine which has antidepressant activity, on intraventricular conduction and the incidence of arrhythmias induced by programmed ventricular stimulation were studied in the dog heart after myocardial infarction and compared to the effects of amitriptyline, a standard tricyclic antidepressant.
Amitriptyline at a dose of 1 mg/kg significantly slowed ventricular conduction in a frequency-dependent manner and at doses of 2 and 3 mg/kg significantly slowed ventricular conduction in infarcted ventricular myocardium. Amitriptyline also significantly slowed ventricular conduction in normal myocardium. Amitriptyline increased the incidence of ventricular arrhythmias induced by the programmed ventricular stimulation and prolonged the intraventricular delayed conduction resulting in re-entrant ventricular arrhythmia.
On the other hand, mianserin and adinazolam at doses of 1–3 mg/kg had no significant effects on intraventricular conduction in infarcted and normal myocardium and on the incidence of arrhythmias induced by programmed ventricular stimulation. From these results, we can expect that mianserin and adinazolam may have a much lower cardiac toxicity than amitriptyline.
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References
Amsterdam JD, Kaplan M, Potter L, Bloom L, Rickels K (1986) Adinazolam, a new triazolobenzodiazepine, and imipramine in the treatment of major depressive disorder. Psychopharmacol 88:484–488
Barth N, Manus M, E (1975) Arrhythmias and inhibition of noradrenaline uptake caused by tricyclic antidepressants and chlorpromazine on the isolated perfused rabbit heart. Naunyn-Schmiedeberg's Arch Pharmacol 288:215–231
Barth N, Muscholl E (1974) The effects of the tricyclic antidepressants desipramine, doxepine and iprindole on the isolated perfused rabbit heart. Naunyn-Schmiedeberg's Arch Pharmacol 284:215–232
Baum T, Shropshire AT, Rowles G, Gluckman MI (1971) Antidepressants and cardiac conduction: iprindole and imipramine. Eur J Pharmacol 13:287–291
Baumann PA, Maitre L (1977) Blockade of presynaptic α-receptors and of amine uptake in the rat brain by the antidepressant mianserine. Naunyn-Schmiedeberg's Arch Pharmacol 300:31–37
Burgess CD, Turner P (1978) Cardiovascular responses to mianserin hydrochloride: A comparison with tricyclic antidepressant drugs. Br J Clin Pharmacol 5 (Suppl 1):21S–28S
Coppen A, Gupta R, Montgomery S, Ghose K, Bailey J, Burns B, De Ridder JJ (1976) Mianserin hydrochloride: A novel antidepressant. Br J Psychiat 129:342–345
Coppen A, Kopera H (1978) Workshop on the clinical pharmacology and efficacy of mianserin. Br J Clin Pharmacol 5 (Suppl 1):91S–99S
Coull DC, Crooks J, Dingwall-Fordyce I, Scott AM, Weir RD (1970) A method of comonitoring drugs for adverse reaction. II. Amitriptyline and cardiac disease. Eur J Clin Pharmacol 3:51–55
Edwards JG, Goldie A (1983) Mianserin, maprotiline and intracardiac conduction. Br J Clin Pharmacol 15 (Suppl 2):249S–254S
El-Sherif N, Scherlag BJ, Lazzara R, Hope RR (1977a) Re-entrant ventricular arrhythmias in the late myocardial infarction period. 1. Conduction characteristics in the infarction zone. Circulation 55:686–702
El-Sherif N, Hope RR, Scherlag BJ, Lazzara R (1977b) Re-entrant ventricular arrhythmias in the late myocardial infarction periods. 2. Patterns of initiation and termination of re-entry. Circulation 55:702–719
Feighner JP (1986) A review of controlled studies of adinazolam mesylate in patients with major depressive disorder. Psychopharmacol Bull 22:186–191
Ghose K, Coppen A, Turner P (1976) Autonomic actions and interactions of mianserin hydrochloride and amitriptyline in patients with depressive illness. Psychopharmacol 49:201–204
Harper B, Hughes IE (1977) A comparison in rabbit isolated hearts of the dysrhythmogenic potential of amitriptyline, maprotiline and mianserin in relation to their ability to block noradrenaline uptake. Br J Pharmacol 59:651–660
Harris AS (1950) Delayed development of ventricular ectopic rhythm following experimental coronary occlusion. Circulation 1:1318–1329
Hopman H (1980) Mianserin, out-patients with depressive illness, in dosage up to 130 mg daily. Curr Med Res Opin 6 (Suppl 7) 107–114
Junien JL, Lakatos C, Padioleau F (1976) Studies of the effects of imipramine on cardiac conduction in anesthetized dogs by His bundle electrogram recording. J Cardiovasc Pharmacol 7:133–138
Kopera RA (1980) Cardiac effects of mianserin: results of clinical pharmacological investigation. Curr Med Res Opin 6:36–42
Lahti RA, Pyke RE, Sethy VH (1984) Adinazolam, a triazolobenzodiazepine antidepressant. Preclinical and clinical data. In: IUPHAR 9th International Congress of Pharmacology. The Macmillan Press, London, abstract 1983P
Marshall JB, Forker AD (1982) Cardiovascular effects of tricyclic antidepressant drugs: Therapeutic usage, overdose, and management of complications. AM Heart J 103:401–414
Matsuo S (1967) Comparative effects of imipramine and propranolol on the transmembrane potentials of the isolated rabbit's atria. Jap J Pharmacol 17:279–286
Moir OC, Cornwell WB, Dingwall-Fordyce I, Crooks J, O'Malley K, Turnbull MJ (1972) Cardiotoxicity of amitriptyline. The Lancet 2:561–564
Montgomery S (1983) Advances with antidepressants: clinical experiences with mianserin. Act Psychiat Scand 67 (Suppl. 305):90–94
Nattel S (1985) Frequency-dependent effects of amitriptyline on ventricular conduction and cardiac rhythm in dogs. Circulation 72:1423–1428
Nishimoto M, Hashimoto H, Ozaki T, Nagashima S, Nakashima M (1989) Comparative effects of antidepressants, amitriptyline, mianserin and adinazolam, on hemodynamics and ECG in myocardial infarcted dogs. Arch Int Pharmacodyn Ther 299:98–109
Pyke RE, Cohn JB, Feighner JP, Smith WT (1983) Open-label studies of adinazolam in severe depression. Psychopharmacol Bull 19:96–98
Turmel A, De Montigny C (1984) Sensitization of rat forebrain neurons to serotonin by adinazolam, an antidepressant triazolobenzodiazepine. Eur J Pharmacol 99:241–244
Vohra J, Burrows G, Hunt D, Sloman G (1975) The effects of toxic and therapeutic doses of tricyclic antidepressant drugs on intracardiac conduction. Eur J Cardiol 3:219–227
Wester HA, Siegers CP (1980) Cardiovascular effects of mianserin and amitriptyline in healthy volunteers. Int J Clin Pharmac Biopharmacy 18:513–517
Wishnie HA, Hackett TP, Cassem NH (1970) Psychological hazards of convalescence following myocardial infarction. JAMA 215:1292–1298
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Department of Pharmacology, Hamamatsu University School of Medicine, 3600, Handa-cho, 431-31, Hamamatsu, Japan
M. Nishimoto, H. Hashimoto, T. Ozaki, S. Nagashima & M. Nakashima
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Nishimoto, M., Hashimoto, H., Ozaki, T.et al. Effects of antidepressants on the intraventricular conduction and the incidence of arrhythmias induced by programmed ventricular stimulation in the dog heart after myocardial infarction.Naunyn-Schmiedeberg's Arch Pharmacol341, 240–245 (1990). https://doi.org/10.1007/BF00169737
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