Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gabapentin (1-50 mg/kg, intraperitoneally (i.p.)) was able to antagonize audiogenic seizures in Dilute Brown Agouti DBA2J (DBA/2) mice in a dose-dependent manner. Gabapentin at dose of 2.5 mg/kg i.p., which per se did not significantly affect the occurrence of audiogenic seizures in DBA/2 mice, potentiated the anticonvulsant activity of carbamazepine, diazepam, felbamate, lamotrigine, phenytoin, phenobarbital and valproate against sound-induced seizures in DBA/2 mice. The potentiation induced by gabapentin was greatest for diazepam, phenobarbital and valproate, less for felbamate and phenytoin and least for carbamazepine and lamotrigine. The increase in anticonvulsant activity was associated with a comparable increase in motor impairment. However, the therapeutic index of combined treatment of the above drugs + gabapentin was more favourable than that of the same drugs + saline. Since gabapentin did not significantly influence the total and free plasma levels of the anticonvulsant drugs studied, we suggest that pharmacokinetic interactions, in terms of total or free plasma levels, are not probable. However, the possibility that gabapentin can modify the clearance from the brain of the anticonvulsant drugs studied can not be excluded. In addition, gabapentin did not significantly affect the hypothermic effects of the anticonvulsants tested. In conclusion, gabapentin showed an additive effect when administered in combination with certain classical anticonvulsants, most notably diazepam, phenobarbital, felbamate, phenytoin and valproate.
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PMID:Gabapentin potentiates the antiseizure activity of certain anticonvulsants in DBA/2 mice. 967 Oct 96

The anti-epileptic, anti-hyperalgesic, and anxiolytic agent gabapentin (1-(aminomethyl)-cyclohexane acetic acid or Neurontin) has previously been shown to bind with high affinity to the alpha2delta subunit of voltage-dependent calcium channels (Gee, N. S. , Brown, J. P., Dissanayake, V. U. K., Offord, J., Thurlow, R., and Woodruff, G.N. (1996) J. Biol. Chem. 271, 5768-5776). We report here the cloning, sequencing, and deletion mutagenesis of the alpha2delta subunit from porcine brain. The deduced protein sequence has a 95.9 and 98.2% identity to the rat and human neuronal alpha2 delta sequences, respectively. [3H]Gabapentin binds with a KD of 37.5 +/- 10.4 nM to membranes prepared from COS-7 cells transfected with wild-type porcine alpha2 delta cDNA. Six deletion mutants (B-G) that lack the delta polypeptide, together with varying amounts of the alpha2 component, failed to bind [3H]gabapentin. C-terminal deletion mutagenesis of the delta polypeptide identified a segment (residues 960-994) required for correct assembly of the [3H]gabapentin binding pocket. Mutant L, which lacks the putative membrane anchor in the delta sequence, was found in both membrane-associated and soluble secreted forms. The soluble form was not proteolytically cleaved into separate alpha2 and delta chains but still retained a high affinity (KD = 30.7 +/- 8.1 nM) for [3H]gabapentin. The production of a soluble alpha2delta mutant supports the single transmembrane model of the alpha2 delta subunit and is an important step toward the large-scale recombinant expression of the protein.
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PMID:Cloning and deletion mutagenesis of the alpha2 delta calcium channel subunit from porcine cerebral cortex. Expression of a soluble form of the protein that retains [3H]gabapentin binding activity. 973 15