Add time:08/19/2019         Source:sciencedirect.com

Attempts were made to find whether [3H]batrachotoxinin A 20-α-benzoate provides a specific probe for measuring interactions of local anesthetics with the sodium channel complex. [3H]Batrachotoxinin A 20-α-benzoate binding, [14C]guanidine and 22Na uptake were investigated in rat brain crude synaptosomal preparations and the potencies of drugs belonging to various chemical and pharmacological classes were compared. The results show that [14C]guanidine uptake seems to be a good model for measuring Na+ fluxes. An allosteric interaction between site 2 and 3 of the Na+ channel is apparent since (i) scorpion venom was able to increase further the guanidine or Na+ stimulation of site 2 toxins to a maximal level and (ii) in the presence of scorpion venom, binding of [3H]BTX-B to site 2 of the Na+ channel was enhanced. A good correlation exists between drug potencies in the binding and uptake experiments. Inhibition by drugs was not restricted to drugs known as local anesthetics. It can be concluded that many drugs seem to interfere with the Na+ channel of rat brain. This may play a role not only in the major effects of local anesthetic drugs but also in the side-effects of drugs from other classes.

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