[Synthesis and biological activity of 7,8-dihydro derivatives of batrachotoxinin interacting with fast sodium channels].

: 7,8-Dihydrobatrachotoxinin (A) (I) was synthesized from 11 alpha-hydroxyprogesterone (III) by a 37-stage procedure. Trimethylpyrrolcarboxylate, benzoate as well as 2-azido-benzoate derivatives of (I) were obtained by mixed anhydride technique, the latter two derivatives being prepared also with tritium atoms in aromatic rings (sp. radioactivity about 28 Cu/mmol). Upon interaction with rat brain synaptosomes the apparent Kd of 7,8-dihydrobatrachotoxinin A 20 alpha-[4-3H]benzoate (Iv) was about 2,5 x 10(-6) M. The (Iv) specific binding was inhibited by aconitine with K0,5 = 1,3 x 10(4) M. Anemonia sulcata toxin II (ATX II) enhanced (Iv) affinity for the receptor up to 7 x 10(-7) M, the maximum binding capacity being 2,5 pmol/mg of protein. Benzocaine and tetracaine competitively displaced specifically bound toxin with K0,5 = 3,1 x 10(-4) M and 5,7 x 10(-7) M, respectively, in the presence of 10(-5) M ATX II. 2-Azido[5-3H]benzoate derivative (Id) was shown to be an effective probe for covalent labeling of the alkaloid toxin receptor of the sodium channel.