PICOLINIC-ACID AND INDOLE-2-CARBOXYLIC ACID - 2 TYPES OF GLYCINERGIC COMPOUNDS MODULATE MOTOR FUNCTION DIFFERENTIALLY

1. A putative agonist for the strychnine-sensitive glycine receptor pi colinic acid was tested for its anticonvulsant activities in mice and muscle-relaxant activities in rats and compared with indole 2-carboxyl ic acid (I2CA), an antagonist for the strychnine-insensitive glycine r eceptor. Their effects on segmental reflexes in the cat spinal cord we re examined to elucidate their sites of action. 2. Picolinic acid (200 and 400 mg/kg IP) delayed the onsets of strychnine- but not pentylene tetrazole-induced seizures. It delayed the onsets of bicuculline-induc ed seizures only at the higher dose. I2CA (200 and 400 mg/kg IP) delay ed the onsets of these 3 kinds of seizures. Both compounds reduced mus cle tone in rat decerebrate rigidity at a dose of 100 mg/kg IV. 3. Pic olinate methylester, a picolinate derivative with higher lipophilicity , depressed spinal reflexes in both intact and spinalized cats at cumu lative doses of 25 to 200 mg/kg IV. I2CA (50 mg/kg IV) inhibited spina l reflexes only in intact preparations. 4. These results suggest that the anticonvulsant and muscle-relaxant activities of piolinic acid (PA ) are due to inhibition of spinal neurons, but that I2CA selectively a ffects supraspinal structures. (C) 1997 Elsevier Science Inc.