The relative ability of the enantiomers of the ethyl and m-nitrophenyl
esters of
nipecotic acid to block convulsions induced by
bicuculline and
pentylenetetrazol, as well as to block the uptake of
GABA into whole brain mini-slices, was studied in mice. Neither (+)
ethyl nipecotate hydrogen tartrate [(+)E.
Tartrate], which is hydrolyzed to (-)
nipecotic acid, nor (-)
ethyl nipecotate hydrogen tartrate [(-)E.
Tartrate], which is hydrolyzed to (+)
nipecotic acid, provided protection against challenge with
bicuculline. Both (+)E.
Tartrate and (-)
ethyl nipecotate hydrochloride [(-)E.HCl], which are hydrolyzed to (-)
nipecotic acid, blocked
seizures induced by
pentylenetetrazol. However, neither (-)E.
Tartrate nor (+)
ethyl nipecotate hydrochloride [(+)E.HCl], which are hydrolyzed to (+)
nipecotic acid, provided significant protection against challenge with
pentylenetetrazol. These results agree with the relative ability of these compounds to inhibit the uptake of
GABA, where (-)
nipecotic acid was more potent than (+)
nipecotic acid and (+)E.
Tartrate was more potent than (-)E.
Tartrate. The enantiomers of m-nitrophenyl-3-piperidinecarboxylate hydrochloride, (+)
MNPC.HCl and (-)
MNPC.HCl, were almost equi-effective in preventing
seizures induced by
bicuculline. This lack of significant difference in
anticonvulsant activity is in contrast with the ability to inhibit the uptake of
GABA, where (-)
MNPC.HCl was significantly more potent than (+)
MNPC.HCl. Changing the route of administration from subcutaneous to
intraperitoneal injection reduced the onset of time of the peak effect and the
anticonvulsant potency of (+/-)
MNPC.HCl.
Cholinergic effects were observed with the administration of (+)E.
Tartrate and (-)E.HCl, but not with (-)E.
Tartrate, (+)E.HCl, (+)
MNPC.HCl or (-)
MNPC.HCl.(ABSTRACT TRUNCATED AT 250 WORDS)