Effect of calcium chloride and 4-aminopyridine therapy on desipramine toxicity in rats.
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. CaCl2 and 4-aminopyridine. Anesthetized rats received the tricyclic antidepressant desipramine IP to produce hypotension, QRS prolongation, and bradycardia. Fifteen min later, animals received CaCl2, NaHCO3, or saline. In a second experiment, rats received tricyclic antidepressant desipramine IP followed in 15 min by 4-aminopyridine or saline.


RESULTS
NaHCO3 briefly (5 min) reversed hypotension and QRS prolongation. CaCl2 and 4-aminopyridine failed to improve blood pressure. The incidence of ventricular arrhythmias (p = 0.004) and seizures (p = 0.03) in the CaCl2 group was higher than the other groups.


CONCLUSIONS
The administration of CaCl2 or 4-aminopyridine did not reverse tricyclic antidepressant-induced hypotension in rats. CaCl2 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.
Wananukul
W
W
Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
Keyler
D E
DE
Pentel
P R
PR
D015761:4-Aminopyridine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage / Q000633:toxicity*; D001145:Arrhythmias, Cardiac / Q000139:chemically induced; D001794:Blood Pressure / Q000187:drug effects; D001919:Bradycardia / Q000188:drug therapy; D015220:Calcium Channels / Q000187:drug effects; D002122:Calcium Chloride / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D003891:Desipramine / Q000008:administration & dosage / Q000633:toxicity*; D004195:Disease Models, Animal; D004562:Electrocardiography / Q000187:drug effects; D007022:Hypotension / Q000139:chemically induced / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D051381:Rats; D012462:Saline Solution, Hypertonic / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D017693:Sodium Bicarbonate / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use
D000929:Antidepressive Agents, Tricyclic; D015220:Calcium Channels; D012462:Saline Solution, Hypertonic; D017693:Sodium Bicarbonate; D015761:4-Aminopyridine; D002122:Calcium Chloride; D003891:Desipramine