Home
Resources
Publications
Differential Interactions of Lamotrigine and Related Drugs With Transmembrane Segment IVS6 of Voltage-Gated Sodium Channels

Differential Interactions of Lamotrigine and Related Drugs With Transmembrane Segment IVS6 of Voltage-Gated Sodium Channels

G Liu, V Yarov-Yarovoy, M Nobbs, J J Clare, T Scheuer, W A Catterall

Neuropharmacology. 2003 Mar;44(3):413-22.

PMID: 12604088

Abstract:

Voltage-gated sodium channels are blocked by local anesthetic and anticonvulsant drugs. A receptor site for local anesthetics has been defined in transmembrane segment S6 in domain IV (IVS6) of the alpha subunit, but the anticonvulsant lamotrigine and related compounds have more complex structures than local anesthetics and may interact with additional amino acid residues. Apparent K(D) values for inactivated-state block of rat brain type IIA sodium channels expressed in Xenopus oocytes were 31.9 micro M, 17.3 micro M, 3.7 micro M and 10.3 micro M for lamotrigine and compounds 227c89, 4030w92 and 619c89, respectively. Compound 619c89 was the strongest frequency-dependent blocker, which correlated with higher affinity and a five-fold slower recovery from drug block compared to lamotrigine. Examination of lamotrigine block of mutant sodium channel alpha subunits, in which alanine had been substituted for each individual amino acid in IVS6, identified mutations I1760A, F1764A and Y1771A as causing the largest reductions in affinity (six-, seven- and 12-fold, respectively). The ratios of effects of these three mutations differed for compounds 227c89, 4030w92, and 619c89. The amino acid residues interacting with these pore-blocking drugs define a surface of IVS6 that is exposed to the pore and may rotate during gating.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP252186791	Lamotrigine Related Compound D		252186-79-1	Price

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: