Anticonvulsant drug action and regional neurotransmitter amino acid changes

1988 ◽  
Vol 72 (3) ◽  
pp. 201-212 ◽  
Author(s):  
A. G. Chapman ◽  
G. P. Hart
Keyword(s):  
Amino Acid ◽  
Anticonvulsant Drug ◽  
Drug Action

Stereochemical basis of anticonvulsant drug action. VI. Crystal and molecular structure of diphenylsilanediol

1977 ◽  
Vol 55 (20) ◽  
pp. 3631-3635 ◽  
Author(s):  
J. Keith Fawcett ◽  
Norman Camerman ◽  
Arthur Camerman
Keyword(s):  
Molecular Structure ◽  
Phenyl Ring ◽  
Anticonvulsant Activity ◽  
Crystal And Molecular Structure ◽  
Anticonvulsant Drug ◽  
Drug Action ◽  
Asymmetric Unit ◽  
Triclinic Space Group ◽  
Fourier Methods ◽  
Cell Dimensions

The crystal and molecular structure of diphenylsilanediol, a compound with recently demonstrated anticonvulsant activity, has been determined and its stereochemistry compared with other antiepileptics. Crystals of diphenylsilanediol are triclinic, space group [Formula: see text] with cell dimensions a = 9.912, b = 15.048, c = 14.519 Å, α = 120.83,β = 99.95, γ = 100.84°, Z = 6 molecules per cell (3 molecules per asymmetric unit). The structure was determined by Patterson and Fourier methods and refined to a final discrepancy value R = 0.034. The phenyl ring planes in the molecule are rotated by 80° with respect to each other, and the hydroxyl oxygen atoms are 2.66 Å apart. The molecular parameters help to delineate limits of stereochemical variation in these molecules with retention of anticonvulsant activity.

scholarly journals Structural requirement of the calcium-channel subunit α2δ for gabapentin binding

1999 ◽  
Vol 342 (2) ◽  
pp. 313-320 ◽  
Author(s):  
Minghan WANG ◽  
James OFFORD ◽  
Dale L. OXENDER ◽  
Ti-Zhi SU
Keyword(s):  
Amino Acid ◽  
Structural Integrity ◽  
Transmembrane Domain ◽  
Anticonvulsant Drug ◽  
Amino Acid Replacement ◽  
Significant Loss ◽  
Single Amino Acid ◽  
Amino Acid Residues ◽  
Structural Requirement ◽  
High Binding Affinity

Gabapentin [Neurontin, 1-(aminomethyl)cyclohexaneacetic acid] is a novel anticonvulsant drug with a high binding affinity for the Ca2+-channel subunit α2δ. In this study, the gabapentin-binding properties of wild-type and mutated porcine brain α2δ proteins were investigated. Removal of the disulphide bonds between the α2 and the δ subunits did not result in a significant loss of gabapentin binding, suggesting that the disulphide linkage between the two subunits is not required for binding. Singly expressed α2 protein remained membrane associated. However, α2 alone was unable to bind gabapentin, unless the cells were concurrently transfected with the expression vector for δ, suggesting that both α2 and δ are required for gabapentin binding. Using internal deletion mutagenesis, we mapped two regions [amino acid residues 339-365 (δF) and 875-905 (δJ)] within the α2 subunit that are not required for gabapentin binding. Further, deletion of three other individual regions [amino acid residues 206-222 (δD), 516-537 (δH) and 583-603 (δI)] within the α2 subunit disrupted gabapentin binding, suggesting the structural importance of these regions. Using alanine to replace four to six amino acid residues in each of these regions abolished gabapentin binding. These results demonstrate that region D, between the N-terminal end and the first putative transmembrane domain of α2, and regions H and I, between the putative splicing acceptor sites (Gln511 and Ser601), may play important roles in maintaining the structural integrity for gabapentin binding. Further single amino acid replacement mutagenesis within these regions identified Arg217 as critical for gabapentin binding.

scholarly journals Cellular Bases of Barbiturate and Phenytoin Anticonvulsant Drug Action

Epilepsia ◽  
1982 ◽  
Vol 23 (s1) ◽  
pp. S7-S18 ◽  
Author(s):  
Robert L. Macdonald ◽  
Michael J. McLean
Keyword(s):  
Anticonvulsant Drug ◽  
Drug Action

Mechanisms of anticonvulsant drug action

1987 ◽  
Vol 146 (1) ◽  
pp. 8-14 ◽  
Author(s):  
C. L. Faingold ◽  
R. A. Browning
Keyword(s):  
Anticonvulsant Drug ◽  
Drug Action
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