On the anticonvulsant activity of kaurenic acid.
Kaurenic acid [(-)-kaur-16-en-19-oic acid] is a diterpene isolated from the aerial parts of Espeletia semiglobulata, one of 85 species of Espeletiinae found in Venezuela. Its anticonvulsive activity was studied using two different models of experimental seizures: spinal seizures induced by sudden cooling (SSSC) in amphibians and seizures induced by pentylenetetrazol (PTZ) in mice. In SSSC, kaurenic acid (KA) inhibited the tonic hind-limb extension with an ED50 of 2.5 mg/kg. It was 4-fold more potent than known anticonvulsant drugs such as carbamazepine and phenytoin and 100-fold more potent than valproic acid. However, KA as well as valproic acid were ineffective against the clonic phase of SSSC. In the PTZ-induced seizures, KA at doses of 0.625 and 1.25 mg/kg increased the latency of seizure onset and protected against generalized clonic-tonic seizures by 45% and 65%, respectively. The sedative effects of KA had an ED50 of 8.5 mg/kg in mice and 75 mg/kg in amphibians. This work provides experimental evidence supporting the potential value of kaurenic acid as an anticonvulsive drug.
Daló
Nelson L
NL
Research Unit Dr. H. Moussatché, School of Veterinary Medicine, Universidad Centroccidental Lisandro Alvarado, Barquisimeto, Venezuela. nelsondalo@yahoo.com
Sosa-Sequera
Miriam C
MC
Usubillaga
Alfredo
A
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity; D002024:Bufo marinus; D003080:Cold Temperature / Q000009:adverse effects; D004195:Disease Models, Animal; D004224:Diterpenes / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity; D004353:Drug Evaluation, Preclinical; D006614:Hindlimb / Q000294:innervation; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D018908:Muscle Weakness / Q000139:chemically induced; D010433:Pentylenetetrazole / Q000633:toxicity; D012021:Reflex, Abnormal / Q000187:drug effects; D012640:Seizures / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control; D013116:Spinal Cord / Q000187:drug effects
D000927:Anticonvulsants; D004224:Diterpenes; C014341:argyrophilic acid; D010433:Pentylenetetrazole