Anticonvulsant activity of dapsone analogs. Electrophysiologic evaluation.
BACKGROUND
In a previous study we reported that 4,4'diaminodiphenylsulfone (dapsone) has anticonvulsant activity using kainic acid (KA) model. This work shows the behavioral and electrophysiologic changes caused by systemic application of several dapsone derivatives. These derivatives include disodium salt of 4,4'-diaminodifenylsulfone N,N'-diformaldehyde sulfoxylate (I), 4,4'-diaminodiphenylsulfone N,N'-didextrose sulfonate (II), sodium dibisulfite 4,4'-biscinamilidenamindiphenyl sulfone (III), and N,N'-dimethyl-4,4'-dimethylphenylsulfone (IV), which were synthesized and purified in our laboratory.


METHODS
A KA model was used to provoke limbic seizures. Limbic seizures were provoked by injection, KA, and electrophysiologic recorder at the following concentrations: 6.25 and 12.50 mg/kg of III and 6.25 and 12.50 mg/kg of IV.


RESULTS
Compounds III and IV caused decrease of postdischarges; we found percentage of protection of 55.60 and 70.78%, respectively. This showed possible anticonvulsant activity of these compounds (III and IV), while I and II showed no significant changes. We also studied whether there was a dose-dependence relationship, and different doses of compound IV were evaluated (25.00, 12.50, 6.25, 3.12, and 1.62 mg/kg). We found that greatest anticonvulsant effect occurred using doses of 3.12 and 6.25 mg/kg (two of the three lowest doses).


CONCLUSIONS
We concluded that IV at doses of 3.25 and 6.25 mg/kg has anticonvulsant effect because it diminished duration of the first limbic seizure induced by KA; latency of first limbic seizure crisis was also increased. Both facts demonstrated possible therapeutic application of compound IV as anticonvulsant.
López-Naranjo
Francisco
F
Departamento de Sistemas Biológicas, División de Ciencias Biológicas y de la Salud, Universidad Autónoma Metropolitana, Unidad Xochimilco, Mexico City, Mexico. angelfra25@hotmail.com
Castañeda-López
Claudia
C
Rojas-Oviedo
Irma
I
Altagracia-Martínez
Marina
M
Krazov-Jinich
Jaime
J
Manjarrez-Marmolejo
Joaquín
J
Alvarado-Calvillo
Raúl
R
D000704:Analysis of Variance; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000927:Anticonvulsants / Q000494:pharmacology*; D003622:Dapsone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D004594:Electrophysiology / Q000379:methods*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D007608:Kainic Acid / Q000378:metabolism; D008297:Male; D008956:Models, Chemical; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000927:Anticonvulsants; D018690:Excitatory Amino Acid Agonists; D003622:Dapsone; D007608:Kainic Acid