A new parasympathomimetic agent: 1-methyl-5-chloroindoline methylbromide.

During the investigations of the effect of indoline-derivatives on the smooth muscle have been continued, we have discovered that 1-methyl-5-chloroindoline methylbromide (hereafter referred to as S-6) well contracts the isolated ileum of guinea pig. Thus, the mode of action of S-6 on the guinea pig ileum has been investigated under various con ditions. The aim of this paper is to show that S-6 contracts the isolated ileum of the guinea pig possibly by acting on acetylcholine receptor directly. METHODS Isolated organs: Segments of the ileum isolated from male guinea pigs were sus pended in a 10 ml organ bath filled with Tyrode solution at 32 C and gassed with a mixture of 95 O., and 5" CO.,. Rectus abdominis muscles isolated from female frogs (Rana nigronracttlata) were suspended in a similar organ bath filled with Ringer solution at 26 C. Responses of the preparations to drugs were recorded on a running drum through an isotonic lever. All results were collected from at least ten experiments. The agonistic activity of a drug was expressed as pD, values or the negative logarithm of the concentration which produced 50(l)) of the maximal response of the muscle. The competitive antagonistic activity of a drug was expressed as the pA., values, which were calculated from the parallel shift of a concentration-action curve of the agonist (1, 2). Coaxial stimulation of ileum: Electrical stimulation of the ileum from the guineaa pig was carried out according to the previous reports (3-5). Rectangular current pulses I msec duration and of sufficient strength to produce a moderate contraction to a single shock were applied to the electrode; the intraluminal electrode was used as the anode. Inhibition of cholinesterase actirit .r: Rat brain homogenate was used as an enzyme source. Acetylcholine (10' g/ml) and brain homogenate was incubated for varying periods in Ringer solution (final 10 ml) at 37 C. Undecomposed acetylcholine was determined on the eserinized rectus abdominis muscles of frogs. Inhibitors were added to the in cubation mixture simultaneously with acetylcholine (6).