Mechanism of action of the spasmogenic activity of penthylenetetrazol and of 1,2,3,4-tetrahydroisoquinolines on rat stomach fundus strips.

Spasmogenic activity of penthylenetetrazol (PTZ) and 1,2,3,4-tetrahydro-isochinoline (THI) derivatives was gradually reduced during storage of their solutions as tested on rat isolated stomach fundus strips. Spasmogenic activity of both PTZ and THI derivatives could be modified by prior exposure of the solutions to electrostatic field and to rotating magnetic field or ultrasound treatment. As a consequence of rotating magnetic field treatment, ED50 values for 1-phenyl-6,7-dimethoxy-1,2,3,4-tetrahydro-isochinoline-hydrochloride (S-23), PTZ and for PTZ crystallized from an ether solution of PTZ (PTZA) doubled, i.e. their activity was reduced by 50 per cent. After an exposure to rotating magnetic field, intrinsic activity of S-23 fell only by 10 to 20 per cent, while after the same treatment the fall in intrinsic activity of PTZ was more pronounced (40 to 50 per cent). Activity of PTZA changed similarly as that of PTZ. Activity of S-23 was similarly modified by exposure of its solution to electrostatic or rotating magnetic field. On the other hand, intrinsic activity of PTZ solution exposed to electrostatic field was twice as high as that of the control PTZ solution. Affinity and intrinsic activity of PTZ solutions diminished after ultrasound treatment. The fall in the activity of PTZ solution of low concentration was greater after the same ultrasound treatment, but its convulsive activity measured in vivo remained unchanged. Spasmogenic activity of ultrasound-treated PTZ reappeared after the solution had been dried under vacuum and then the residue crystallized and redissolved in water. These findings allow the conclusion that the observed changes in activity could be the result of spontaneous or field-evoked alterations in molecular state (orientation, association etc.) conformation. The fact that the activity of PTZ solution measured in vivo did not change during storage supports this assumption.