In-vitro evaluation of filaricidal activity of GABA and 1,3-dipalmitoyl-2-(4-aminobutyryl)glycerol HCl: a diglyceride prodrug.
A diglyceride ester of gamma-aminobutyric acid (GABA) has been synthesized and its filaricidal activity compared with GABA, and progabide in-vitro, on infective larvae and microfilariae of Molinema dessetae, a rodent filaria. GABA induced paralysis in infective larvae but was inactive on microfilariae. There were interactions between the culture medium and GABA. The ester drug at 0.1 mmol L-1 (1,3-dipalmitoyl-2-(4-aminobutyryl)glycerol HCl) was as active as progabide on infective larvae and hundredfold more potent than GABA. Its microfilaricidal activity at 1 mmol L-1 was lower than that progabide at 0.1 mmol L-1 but a delayed effect was observed. The data confirm filariae sensitivity to GABA derivatives.
Deverre
J R
JR
Laboratoire de Pharmacie Galénique et de Biopharmacie, UA CNRS, Université de Paris XI, Chatenay-Malabry, France.
Loiseau
P
P
Couvreur
P
P
Letourneux
Y
Y
Gayral
P
P
Benoit
J P
JP
D000818:Animals; D000871:Anthelmintics; D005369:Filaricides; D005370:Filarioidea / Q000187:drug effects; D008842:Microfilariae / Q000187:drug effects; D011355:Prodrugs; D014280:Triglycerides / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives / Q000032:analysis / Q000494:pharmacology*
D000871:Anthelmintics; D005369:Filaricides; D011355:Prodrugs; D014280:Triglycerides; C060252:1,3-dipalmitoyl-2-(4-aminobutyryl)glycerol; C017985:progabide; D005680:gamma-Aminobutyric Acid