Interaction of zonisamide with benzodiazepine and GABA receptors in rat brain.
The effects of zonisamide on [3H]flunitrazepam binding and [3H]muscimol binding were studied in Sprague-Dawley rat brain. Specific [3H]flunitrazepam bound was decreased to 64.6 +/- 5.6% (mean +/- SD, n = 5, p < 0.002) and 91.9 +/- 4.0% (p < 0.005) by the addition of 10(-3) M and 10(-4) M zonisamide, respectively. Scatchard plot analysis of [3H]flunitrazepam binding with 10(-3) M of zonisamide revealed an increased Kd value with no change in Bmax. No inhibitory effect of zonisamide was seen on the enhancement of specific [3H]flunitrazepam binding by GABA. As for the effects on GABA receptors, specific [3H]muscimol bound was decreased to 27.7 +/- 10.4% (mean +/- SD, n = 4, p < 0.005) and 68.3 +/- 3.7% (mean +/- SD, n = 4, p < 0.005) by the addition of 10(-3) M and 10(-4) M zonisamide, respectively. Since therapeutic serum level of zonisamide are around 10(-4) M, these results suggest that zonisamide neuropharmacologically interacts with the GABA/benzodiazepine receptor ionophore complex in a manner similar to phenytoin.
Department of Pediatrics, Osaka University Medical School, Japan.
T
T
Mimaki
Y
Y
Suzuki
T
T
Tagawa
T
T
Karasawa
H
H
Yabuuchi
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005445:Flunitrazepam / Q000378:metabolism; D007555:Isoxazoles / Q000494:pharmacology*; D008297:Male; D009118:Muscimol / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018079:Receptors, GABA / Q000187:drug effects / Q000378:metabolism*; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism; D013570:Synaptic Membranes / Q000187:drug effects / Q000378:metabolism; D000078305:Zonisamide
D000927:Anticonvulsants; D007555:Isoxazoles; D018079:Receptors, GABA; D011963:Receptors, GABA-A; D009118:Muscimol; D000078305:Zonisamide; D005445:Flunitrazepam