Anticonvulsant action of a new analogue of allopregnanolone in immature rats.
Neuroactive steroids represent potential antiepileptic drugs. We tested a newly synthesized analogue of allopregnanolone 3alpha-hydroxy-21xi,22-oxido-21-homo-5alpha-pregnan-20-on (HOHP) against two types of pentylenetetrazol-induced seizures (100 mg/kg s.c.) in 12- and 25-day-old rats. Ganaxolone, a neuroactive steroid in clinical trials, served as a reference drug. Pretreatment with either steroid suppressed generalized tonic-clonic seizures in both age groups, their efficacy was comparable. HOHP as well as ganaxolone were more active in 12- than in 25-day-old rats (effective doses were 40 and 60 mg/kg, respectively). Minimal clonic seizures, which can be elicited only in 25-day-old rats, were not influenced by any drug. Very short duration of anticonvulsant action of HPOP demonstrated in 12-day-old animals indicates that this drug might be used only in acute treatment in epileptology.
Mares
P
P
Department of Developmental Epileptology, Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic. maresp@biomed.cas.cz
Kubová
H
H
Kasal
A
A
D000208:Acute Disease; D000367:Age Factors; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D004830:Epilepsy, Tonic-Clonic / Q000188:drug therapy*; D011280:Pregnanolone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D051381:Rats
C551091:3alpha-hydroxy-21epsilon,22-oxido-21-homo-5alpha-pregnan-20-one; D000927:Anticonvulsants; C105051:ganaxolone; D011280:Pregnanolone