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Background: Hypotension is a major contributor to mortality in tricyclic antidepressant overdose. Recent data suggest that tricyclic antidepressants inhibit calcium influx in some tissues. This study addressed the potential role of calcium channel blockade in tricyclic antidepressant-induced hypotension. Methods: Two interventions were studied that have been shown previously to improve blood pressure with calcium channel blocker overdose. [CaCl.sub.2] and 4-aminopyridine. Anesthetized rats received the tricyclic antidepressant desiprarmine IP to produce hypotension, QRS prolongation, and bradycardia. Fifteen min later, animals received [CaCl.sub.2], [NaHCO.sub.3], or saline. In a second experiment, rats received tricyclic antidepressant desipramine IP followed in 15 min by 4-aminopyridine or saline. Results: [NaHCO.sub.3], briefly (5 min) reversed hypotension and QRS prolongation. [CaCl.sub.2] and 4-aminopyridine failed to improve blood pressure. The incidence of ventricular arrhytmias (p = 0.004) and seizures (p = 0.03) in the [CaCl.sub.2] group was higher than the other groups. Conclusion: The administration of [CaCl.sub.2] or 4-aminopyridine did not reverse tricyclic antidepressant-induced hypotension in rats. [CaCl.sub.2] therapy may possibly worsen both cardiovascular and central nervous system toxicity. These findings do not support a role for calcium channel inhibition in the pathogenesis of tricyclic antidepressant-induced hypotension., INTRODUCTION Hypotension is an important contributor to the mortality of tricyclic antidepressant (TCA) overdose. Major factors believed to be responsible for hypotension include vasodilatation due to alpha adrenergic blockade and [...]

Byline: Paul R Pentel, William Scarlett, Catherine A Ross, John Landon, Ahmed Sidki, Daniel E Keyler Abstract: Study objective: Tricyclic antidepressants (TCAs) are a leading cause of death from intentional drug overdose. Available therapies are often unsatisfactory. In this study we evaluated the use of a high-affinity drug-specific polyclonal Fab fragment (TFab) as an antidote to desipramine toxicity. Design: We gave anesthetized rats under mechanical ventilation IV desipramine so that we might study the effect of TFab on survival or IP desipramine to facilitate study of the interaction of TFab and hypertonic sodium bicarbonate (NaHCO.sub.3), the standard clinical treatment for TCA overdose. Interventions: For the study of the effects of TFab and NaHCO.sub.3 on survival, each rat was given a constant IV infusion of desipramine until it died, together with TFab 2 g/kg, bovine serum albumin, or .9% NaCl starting 5 minutes after the desipramine infusion. In the study of the interaction of TFab and NaHCO.sub.3, each rat received 30 mg/kg IP desipramine followed by TFab (molar TFab:desipramine ratio, .11), NaHCO.sub.3, TFab+NaHCO.sub.3, or NaCl at the time of maximal toxicity (15 minutes). Results: In the survival protocol, QRS-interval duration, systolic blood pressure, and heart rate were significantly improved by TFab, and survival was prolonged by 58% compared with that in the albumin and NaCl groups (P Article History: Received 15 November 1994; Revised 6 February 1995; Accepted 22 March 1995 Article Note: (footnote) [star] From the Department of Medicine, Hennepin County Medical Center*, the Departments of Medicinea and PharmacologyAs. of the University of Minnesota School of Medicine and the University of Minnesota College of PharmacologyA[paragraph], and the Minneapolis Medical Research Foundationa[yen], Minneapolis, Minnesota; and Therapeutic Antibodies, Incorporated, St Bartholomew's Medical College, London, England.# , [star][star] Supported by US Public Health Service grant MH42799 and Therapeutic Antibodies, Incorporated., a Address for reprints: Paul Pentel, MD, Department of Medicine, Hennepin County Medical Center, 701 Park Avenue, Minneapolis, Minnesota 55415, 612-347-6426, Fax 612-347-2020, aa Reprint no. 47/1/67365