EFFECTS OF DRUGS ON UPTAKE OF ACETYLCHOLINE IN RAT BRAIN CORTEX SLICES

The following drugs inhibit competitively uptake of acetylcholine against a concentration gradient into rat brain cortex slices incubated aerobically at 37° in a physiological saline-glucose medium containing 20 μM paraoxon: eserine (Ki = 0.9 × 10-5M), tetramethylammonium chloride (Ki = 0.4 × 10-5M), tetraethylammonium chloride (Ki = 0.5 × 10-5M), atropine (Ki = 1.8 × 10-5M), cocaine (Ki = 0.33 × 10-5M), procaine (Ki = 0.23 × 10-5M), lidocaine (Ki = 0.09 × 10-5M), chlorprocaine (Ki = 0.5 × 10-5M), methacholine (Ki = 0.4 × 10-5M), succinylcholine (Ki = 0.6 × 10-5M), d-tubocurarine (Ki = 0.6 × 10-5M), hexamethonium (Ki = 1.2 × 10-5M), pilocarpine (Ki = 0.5 × 10-5M), nicotine (Ki = 0.6 × 10-5M), strychnine (Ki = 0.6 × 10-5M), and hemicholinium (Ki = 0.6 × 10-5M). The following drugs inhibit noncompetitively: chlorpromazine and amphetamine. A comparison of the inhibitor constants of a number of these drugs, which act competitively on acetylcholine transport, with the inhibitor constants towards acetylcholine esterase or certain neurophysiological acetylcholine receptor sites leads to the conclusion that the transport carrier site for acetylcholine is not identical in chemical structure with the anionie site of acetylcholine esterase or with the acetylcholine receptor sites. The noncompetitive effects of certain drugs suggest the presence of a site on the transport carrier, with an affinity for these drugs, which affects the reactions of acetylcholine at the brain cell membrane. © 1969.