Isomers of long-chain alkane derivatives and nervous impulse blockage.
The potency to block nervous impulse of members of normal aliphatic homologous series of primary and secondary isomers of functional derivatives of alkanes was tested in bundles of a few axons from sciatic nerves of the toad Bufo marinus. For the primary substituted functional derivates of pentane, the relative potency series was I greater than H approximately equal to Br greater than Cl greater than COOCH3 greater than F greater than CH2OH greater than COCH3 greater than OH approximately equal to NH2 greater than COOH. For the homologous series of primary alkanols, and from saturated Ringer's solutions, the time required to reversibly reduce the amplitude of the action potential to one-half its initial value were determined. The cut-off effect was detected at the level of dodecan-1-ol, while for the primary bromoalkanes it was bromooctane. However, solutions of the secondary isomer of the inactive primary homologues, such as tridecan-5-ol and tridecan-7-ol or 2-bromononane, were able to block nervous impulse conduction reversibly. From the concentration required for an equipotent effect it was calculated that the standard free energy for adsorption of primary alkanols was -705 cal mol- CH2. Similarly, for primary bromoalkanes a value of -733 cal mol-1 CH2 was obtained. The concentration required for an equipotent effect for primary isomer (either of alkanols or bromoalkanes) is lower than those obtained for the secondary isomers. Therefore, the latter are less potent than the former. Among secondary isomers the potency decreases as the functional group is moved away from the terminal carbon. The differential effect of structural isomers of long-chain alkane derivates around the point of cut-off cannot be explained in terms of differences in chemical properties, concentration in aqueous and membrane phases, or mean molecular volume. It is concluded that a volume related to that of the hydrophobic region of the agent and not its mean molecular volume should be responsible for an expansion of the target region.
D000438:Alcohols / Q000494:pharmacology; D000473:Alkanes / Q000494:pharmacology*; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology*; D002024:Bufo marinus; D012584:Sciatic Nerve / Q000187:drug effects / Q000502:physiology*; D013329:Structure-Activity Relationship
D000438:Alcohols; D000473:Alkanes