Interaction of zonisamide with benzodiazepine and GABA receptors in rat brain.

Article date: 1990/3/1

PubMed ID: 1369646

Journal name: Medical journal of Osaka University (ISSN: 0030-6169)


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.

Author List: Mimaki T, Suzuki Y, Tagawa T, Karasawa T, Yabuuchi H

Publication Types: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't

Substances mentioned in the article: Anticonvulsants; Isoxazoles; Receptors, GABA; Receptors, GABA-A; Muscimol; zonisamide; Flunitrazepam;

Mesh terms: Animals; Anticonvulsants/pharmacology; Brain/metabolism; Dose-Response Relationship, Drug; Flunitrazepam/metabolism; Isoxazoles/pharmacology; Male; Muscimol/metabolism; Rats; Rats, Sprague-Dawley; Receptors, GABA/drug effects; Receptors, GABA-A/drug effects; Synaptic Membranes/drug effects;

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