Drug-specific antibodies as antidotes for tricyclic antidepressant overdose.

ABSTRACT

Drug-specific antibodies have been used clinically to treat digoxin or colchicine overdose. The lethal dose of tricyclic antidepressants (TCAs) is 100 times higher, and will require higher doses of antibodies (up to several g/kg) to reverse toxicity. Preliminary studies suggest that this is feasible. High affinity TCA-specific monoclonal Fab' or polyclonal Fab fragments rapidly reverse the cardiovascular toxicity of the TCA desipramine (DMI) in rats, and prolong survival. TCA-specific Fab' or Fab is generally well tolerated in rats, but doses several times higher than anticipated for human use may have adverse effects. Combining Fab with standard therapies for TCA overdose, such as NaHCO3, can reduce the required Fab dose. As an alternative, a recombinant single chain Fv fragment (sFv), one half the size of Fab, has been cloned which retains a high affinity for DMI and is able to alter DMI distribution in vivo. Because sFv has a shorter elimination half-life and more extensive renal excretion than Fab, it may have therapeutic advantages.