HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Reith, M. E. Articles by Lajtha, A. Search for Related Content PubMed PubMed Citation Articles by Reith, M. E. Articles by Lajtha, A. Social Bookmarking                      What's this?

J. Biol. Chem., Vol. 261, Issue 16, 7300-7305, 06, 1986

Structural requirements for cocaine congeners to interact with [3H]batrachotoxinin A 20-alpha-benzoate binding sites on sodium channels in mouse brain synaptosomes

ME Reith, SS Kim and A Lajtha

The present study examines the possible role of sodium channels in the behavioral effects of cocaine. Cocaine congeners are apparent competitive inhibitors of the scorpion toxin-enhanced binding of [3H]batrachotoxinin A 20-alpha-benzoate to sodium channels in mouse cerebrocortical synaptosomes. However, in agreement with the allosteric model for heterotropic cooperative interactions, the compounds produce a concentration-dependent increase in the rate of dissociation of binding. Concentrations that give a 2-fold increase of k-1 are close to Ki values for inhibiting equilibrium binding of [3H]bactrachotoxinin A 20-alpha-benzoate, suggesting that the inhibitory effect on binding results mostly from an increase of the apparent dissociation rate constant. The ester linkage between the tropane and benzoyl ring of cocaine is not essential for the inhibitory potency, and for both the C- 2 and C-3 substituents the equatorial position results in a higher potency than the axial position. There is reasonable agreement between the rank order of potencies in blocking the sodium channel and in inhibiting locomotor behavior. The present results do not support a relationship between the capability of cocaine congeners in blocking sodium flux and in inhibiting uptake of dopamine into striatal synaptosomes. However, peak levels of cocaine in the brain of cocaine addicts could be high enough to interfere with sodium channel functioning, possibly contributing to some of cocaine's actions.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				X.-T. Hu, S. Basu, and F. J. White Repeated Cocaine Administration Suppresses HVA-Ca2+ Potentials and Enhances Activity of K+ Channels in Rat Nucleus Accumbens Neurons J Neurophysiol, September 1, 2004; 92(3): 1597 - 1607. [Abstract] [Full Text] [PDF]

				S. Ikemoto Involvement of the Olfactory Tubercle in Cocaine Reward: Intracranial Self-Administration Studies J. Neurosci., October 15, 2003; 23(28): 9305 - 9311. [Abstract] [Full Text] [PDF]

				X.-F. Zhang, X.-T. Hu, and F. J. White Whole-Cell Plasticity in Cocaine Withdrawal: Reduced Sodium Currents in Nucleus Accumbens Neurons J. Neurosci., January 1, 1998; 18(1): 488 - 498. [Abstract] [Full Text] [PDF]