STUDIES ON THE PHARMACOLOGICAL ACTIONS OF CORYDALIS——Ⅷ.STRUCTURE-ACTIVITY RELATIONSHIP OF ANALOGUES OF CORYDALIS B(TETRAHYDROPALMATINE)

Thirty-eight analogues (Table Ⅰ) of corydalis B (Tetrahydropalmatine) were investigated for their analgesic (radiant heat on rabbits), sedative (potentiation of hexobarbital narcosis) and anticonvulsive (antielectroshock in mice) actions. The results obtained were as follows: (1)Both analgesic and sedative effects were to a considerable extent dependent upon saturation of ring Ⅲ of the nucleus of corydalis B, and diminished or eliminated by (a) substitution of halogen atom on the one of benzene rings; (b) replacement of the 4 methyl groups of ether linkage on benzene rings with the other alkyl or acyl groups; and (c) splitting one of either ring Ⅱ or Ⅲ. Simultaneous splitting of both ring Ⅱ and Ⅲ to form various sympathomimetic-like structure amines, however, brought about a temporary excitation instead of analgesia and sedation. (2)In the same dose of the optic isomers of corydalis B, only the ι-form yielded a significant sedation in sharp contrast to the d-form which produced a temporary excitation. (3)Among these 38 analogues, only tetrahydroberberine showed some valuable sedative property which warrants further investigations. (4)From among 30 analogues no one showed any antielectroshock effect, whilst corydalis B itself revealed a weak effect.