Tarzia G, Occelli E, Corsico N, Luzzani F, Barone D
Merrell-Dow Research Institute, Lepetit Research Centre, Gerenzano, Italy.
Farmaco Sci. 1988 Feb;43(2):189-201.
A series of 3-aryl-6-alkoxy- and some 3-aryl-6-thioalkyl-, 3-aryl-6-alkylsulphinyl-, and 3-aryl-6-alkylsulphonyl-1,2,4-triazolo[3,4-a]phthalazines were synthesised and tested for inhibition of the in vitro binding of 3H-Diazepam to benzodiazepine receptors in membranes isolated from rat brain synaptosomes. 6-Alkoxy-3-(4'-methoxy)phenyl-1,2,4-triazolo[3,4-a]phthalazines were more active than or as active as diazepam in the binding assay (Ki nM) but unlike diazepam their binding to the benzodiazepine receptors was not enhanced by 4-aminobutyric acid. These compounds did not antagonize pentylenetetrazole induced convulsions and were inactive in modifying the conditioned behaviour of rats. Compound (II a) counteracted the muscle relaxant effects of diazepam (traction test). These results suggest that (II a) may be a benzodiazepine receptor antagonist.
合成了一系列3-芳基-6-烷氧基-以及一些3-芳基-6-硫代烷基-、3-芳基-6-烷基亚磺酰基-和3-芳基-6-烷基磺酰基-1,2,4-三唑并[3,4-a]酞嗪，并测试了它们对从大鼠脑突触体分离的膜中3H-地西泮与苯二氮䓬受体体外结合的抑制作用。在结合试验（Ki nM）中，6-烷氧基-3-(4'-甲氧基)苯基-1,2,4-三唑并[3,4-a]酞嗪比地西泮更具活性或与地西泮活性相当，但与地西泮不同的是，它们与苯二氮䓬受体的结合不会被4-氨基丁酸增强。这些化合物不会拮抗戊四氮诱导的惊厥，并且在改变大鼠的条件行为方面没有活性。化合物（II a）抵消了地西泮的肌肉松弛作用（牵引试验）。这些结果表明（II a）可能是一种苯二氮䓬受体拮抗剂。
