Picolinic acid and indole-2-carboxylic acid: two types of glycinergic compounds modulate motor function differentially.
1. A putative agonist for the strychnine-sensitive glycine receptor picolinic acid was tested for its anticonvulsant activities in mice and muscle-relaxant activities in rats and compared with indole-2-carboxylic acid (I2CA), an antagonist for the strychnine-insensitive glycine receptor. Their effects on segmental reflexes in the cat spinal cord were examined to elucidate their sites of action. 2. Picolinic acid (200 and 400 mg/kg IP) delayed the onsets of strychnine- but not pentylenetetrazole-induced seizures. It delayed the onsets of bicuculline-induced seizures only at the higher dose. I2CA (200 and 400 mg/kg IP) delayed the onsets of these 3 kinds of seizures. Both compounds reduced muscle tone in rat decerebrate rigidity at a dose of 100 mg/kg IV. 3. Picolinate methylester, a picolinate derivative with higher lipophilicity, depressed spinal reflexes in both intact and spinalized cats at cumulative doses of 25 to 200 mg/kg IV. I2CA (50 mg/kg IV) inhibited spinal reflexes only in intact preparations. 4. These results suggest that the anticonvulsant and muscle-relaxant activities of picolinic acid (PA) are due to inhibition of spinal neurons, but that I2CA selectively affects supraspinal structures.
Tonohiro
T
T
Neuroscience Research Laboratory, Sankyo Co., Ltd, Tokyo, Japan.
Kaneko
T
T
Tanabe
M
M
Iwata
N
N
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001640:Bicuculline; D002264:Carboxylic Acids; D002415:Cats; D003655:Decerebrate State; D005260:Female; D018684:Glycine Agents / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009126:Muscle Relaxation; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000294:innervation; D010848:Picolinic Acids / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012018:Reflex / Q000187:drug effects*; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy*; D013331:Strychnine
D000927:Anticonvulsants; D002264:Carboxylic Acids; D018684:Glycine Agents; D007211:Indoles; D010848:Picolinic Acids; C058980:indole-2-carboxylic acid; D013331:Strychnine; C030614:picolinic acid; D001640:Bicuculline