New insights in cyclodextrin: surfactant mixed systems from the use of neutral and anionic cyclodextrin derivatives.

The kinetics of the hydrolysis of 4-methoxybenzenesulfonyl chloride (MBSC) have been studied in mixed systems made up of surfactant, sodium dodecyl sulfate (SDS) or tetradecyltrimethylammonium bromide (TTABr), and cyclodextrin, beta-CD or SBE-beta-CD(Captisol). The use of SBE-beta-CD instead of beta-CD allowed us to indicate certain characteristics of the mixed cyclodextrin-surfactant system: (a) The percentage of uncomplexed cyclodextrin is higher for SBE-beta-CD than for beta-CD when we use SDS, but the opposite effect was observed when we use TTABr. This behavior can be explained by taking into account the increase in salinity when we add SBE-beta-CD, and the electrostatic forces between the SBE-beta-CD and the surfactant that have influence on the complexation. (b) The presence or even the charge of cyclodextrin has no effect on the properties of surfactant micelles once they have been formed; in particular, it does not alter K(s)(m) or k(m), parameters very sensitive to the micellar system structure. Therefore, we can conclude that for surfactants concentrations lower than the micellization point, the charge of cyclodextrin modifies the cyclodextrin-surfactant interactions but once the micelles have been formed there is no interaction between them and the cyclodextrins.

N-methylanatoxinol isomers: derivatives of the agonist (+)-anatoxin-a block the nicotinic acetylcholine receptor ion channel.

Using biochemical and patch-clamp techniques, we investigated the pharmacology of S- and R-epimers of N-methylanatoxinol, which are analogs of the semi-rigid, stereoselective, nicotinic agonist (+)-anatoxin-a. In contrast to (+)-anatoxin-a, both isomers had poor ability to inhibit the binding of 125I-alpha-bungarotoxin or to open acetylcholine channels, and they were unable to elicit contracture of frog rectus abdominis muscles. However, both isomers were able to demonstrate significant concentration-dependent blockade of the nicotinic acetylcholine receptor ion channel. The R-isomer was approximately 4-fold more potent in causing inhibition of [3H]H12HTX binding than was the S-isomer, in the absence of carbamylcholine. In the presence of carbamylcholine, the affinity of the R-isomer of N-methylanatoxinol for the ion channel sites was further enhanced, so that its affinity became much greater than that of the S-isomer. Refinement of voltage- and concentration-dependent terms for the ion channel blocking and unblocking rates yielded functions that were able to predict the channel open times and short closed times well. The S-isomer bound and dissociated from the ion channel site of the nicotinic acetylcholine receptor more rapidly and with greater voltage sensitivity than the R-isomer. The present characterization of the antagonistic properties of these new analogs of (+)-anatoxin-a introduces a new aspect to the molecular pharmacology of (+)-anatoxin-a analogs; the semi-rigid compounds could be useful in describing the allosteric binding sites of the acetylcholine receptor, as well as in delimiting the agonist binding site.