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. 2002 Feb;22(1):1–12. doi: 10.1023/A:1015301610349

Reserpine: Interactions with Batrachotoxin and Brevetoxin Sites on Voltage-Dependent Sodium Channels

Andrew Flowers 1, Kenolisa Onwueme 1, Cyrus R Creveling 1, John W Daly 1
PMCID: PMC11533732  PMID: 12064513

Abstract

Reserpine inhibited batrachotoxin-elicited sodium influx in guinea pig brain synaptoneurosomes with an IC50 of about 1 μM. In the presence of brevetoxin the IC50 increased to about 80 μM. Reserpine inhibited binding of batrachotoxinin-A [3H]benzoate ([3H]BTX-B) binding in a complex manner causing a partial inhibition from 0.001 to 0.08 μM, then a rebound stimulation from 0.1 to 0.8 μM, followed by complete inhibition by 80 μM. The stimulation was prevented by the presence of brevetoxin; reserpine then smoothly inhibited binding with an IC50 of about 1 μM. Reserpine at 1 μM slightly reduced the off-rate of [3H]BTX-B binding measured in the presence of veratridine, while at a concentration of 50 μM it enhanced the off-rate, presumably by an allosteric mechanism. Reserpine at 0.3–10 μM elicited a partial inhibition of the binding of [3H]brevetoxin-3. The local anesthetic dibucaine had effects similar to reserpine: It partially inhibited binding of [3H]brevetoxin. The presence of brevetoxin reduced the potency of dibucaine as an inhibitor of batrachotoxin-elicited sodium influx from an IC50 of about 2 μM to an IC50 of about 50 μM. The results suggest that reserpine binds at both a local anesthetic site to cause allosteric inhibition of batrachotoxin-binding and action, but that it also binds to another site causing, like brevetoxin, an enhancement of batrachotoxin-binding and action. Local anesthetics also may bind to the brevetoxin site.

Keywords: sodium channels, batrachotoxin, brevetoxin, reserpine

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