Synergistic effect of phosphatidylserine with gamma-aminobutyric acid in antagonizing the isoniazid-induced convulsions in mice.
The influence of phosphatidylserine (PS) on the isoniazid-induced convulsions has been studied in mice. Sonicated dispersions of this phospholipid given intravenously do not show anticonvulsant activity but they do so when gamma-aminobutyric acid (GABA) is simultaneously injected. GABA alone is inactive. The synergism between PS and GABA is influenced by the structure of the phospholipid liposomes. In contrast to multilamellar vesicles, oligolamellar vesicles are active. Under these conditions the effect shows head group specificity, in that the neutral phosphatidylcholine (PC) or the acidic phosphatidylinositol (PI) are inactive, either in the presence or in the absence of GABA. Lysophosphatidylserine (lysoPS), the deacylated PS derivative, shows increased efficacy as an isoniazid antagonist in the presence of GABA, and has anticonvulsant activity also in the absence of GABA. Other lysophospholipids are inactive. It is suggested that PS, after its metabolic conversion to lysoPS, enhances the anticonvulsant effect of GABA.
D000818:Animals; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D007538:Isoniazid; D008081:Liposomes / Q000008:administration & dosage; D008246:Lysophospholipids; D051379:Mice; D010718:Phosphatidylserines / Q000627:therapeutic use*; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy*; D013010:Sonication; D013329:Structure-Activity Relationship; D005680:gamma-Aminobutyric Acid / Q000627:therapeutic use*
D008081:Liposomes; D008246:Lysophospholipids; D010718:Phosphatidylserines; C025059:lysophosphatidylserine; D005680:gamma-Aminobutyric Acid; D007538:Isoniazid