An alternative antidote therapy in amitriptyline-induced rat toxicity model: theophylline

• Published in: Drug and chemical toxicology (New York, N.Y. 1978) N.Y. 1978), 2011-01, Vol.34 (1), p.53-60
• Main Authors: Oransay, Kubilay, Kalkan, Sule, Hocaoglu, Nil, Arici, Aylin, Tuncok, Yesim
• Format: Article
• Language: English
• Subjects: adenosine; Amitriptyline; Amitriptyline - poisoning; Amitriptyline - toxicity; Animals; Antidotes - administration & dosage; Antidotes - therapeutic use; Blood Gas Analysis; Blood Pressure - drug effects; Carbon Dioxide - blood; Disease Models, Animal; Drug Administration Schedule; Electrocardiography; Glucose - administration & dosage; Glucose - therapeutic use; Heart Rate - drug effects; hypotension; Infusions, Intravenous; Injections, Intravenous; Male; Oxygen - blood; Poisoning - blood; Poisoning - drug therapy; Poisoning - physiopathology; Purinergic P1 Receptor Antagonists - administration & dosage; Purinergic P1 Receptor Antagonists - therapeutic use; QRS prolongation; Rats; Rats, Wistar; theophylline; Theophylline - administration & dosage; Theophylline - therapeutic use; Time Factors
• ISSN: 0148-0545; 1525-6014
• DOI: 10.3109/01480545.2010.495947

We planned this study in order to investigate the effects of theophylline on cardiovascular parameters in an anaesthetized rat model of amitriptyline toxicity. In the preliminary study, we tested theophylline as 1 mg/kg of bolus, followed by a 0.5-mg/kg infusion. Toxicity was induced by the infusion of 0.94 mg/kg/min of amitriptyline up to the point of a 40-45% inhibition of mean arterial pressure (MAP). The rats were randomized to two groups: a group of 5% dextrose bolus followed by 5% dextrose infusion, and another group with theophylline bolus followed by infusion. Amitriptyline caused a significant decrease in MAP and prolongation in QRS; however, it did not alter heart rate (HR). When compared to the dextrose group, theophylline administration increased MAP, shortened prolonged QRS duration, and increased HR (P  0.05). Bolus doses followed by a continuous infusion of theophylline were found to be effective in reversing the hypotension and QRS prolongation seen in amitriptyline toxicity. One of the possible explanations of this beneficial effect is nonselective adenosine antagonism of theophylline. Further studies are needed to reveal the exact mechanism of the observed effect.