Antidepressants and seizure-interactions at the GABA-receptor chloride-ionophore complex.
Convulsive seizures are a potential side effect of antidepressant drug treatment and can be produced by all classes of antidepressants. It is also known that some convulsant and anticonvulsant drug actions are mediated by the GABA-receptor chloride-ionophore complex. Drugs acting at this complex appear to induce convulsions by inhibiting chloride conductance through the associated chloride channel. Using the method of GABA-stimulated 36Cl-uptake by rat cerebral cortical vesicles, we show that some antidepressant drugs (imipramine, amitryptyline, and mianserine) can inhibit the GABA-receptor chloride uptake, and that the degree of chloride channel inhibition by these drugs correlates with the frequency of convulsive seizures induced by them.
Malatynska
E
E
University of Arizona, Department of Pharmacology, Tucson 85724.
Knapp
R J
RJ
Ikeda
M
M
Yamamura
H I
HI
D000639:Amitriptyline / Q000009:adverse effects / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000009:adverse effects* / Q000494:pharmacology; D002540:Cerebral Cortex / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism*; D003891:Desipramine / Q000009:adverse effects / Q000494:pharmacology; D007099:Imipramine / Q000009:adverse effects / Q000494:pharmacology; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism; D007476:Ionophores / Q000378:metabolism*; D008297:Male; D008803:Mianserin / Q000009:adverse effects / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism; D012640:Seizures / Q000139:chemically induced*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000928:Antidepressive Agents; D002712:Chlorides; D007473:Ion Channels; D007476:Ionophores; D011963:Receptors, GABA-A; D000639:Amitriptyline; D008803:Mianserin; D005680:gamma-Aminobutyric Acid; D007099:Imipramine; D003891:Desipramine