TACRINE DOES NOT ALTER THE POTENCY OF SUCCINYLCHOLINE IN THE RAT

Purpose: Tacrine is a cholinesterase inhibitor used to manage Alzheime r's dementia. Given iv, it prolongs succinylcholine blockade in humans but the effects of chronic oral tacrine are not known. Methods: Group s of adult rats were given 2.5 mg.kg(-1) tacrine (chronic groups) or 1 ml saline (control) twice daily by gavage for one, two, four or eight weeks. An additional (acute) group received 2.5 mg.kg(-1) tacrine iv. Twelve to 18 hr after the last gavage of tacrine or saline, and simil ar to 20 min after iv tacrine, cumulative dose-response curves of succ inylcholine were determined in the tibialis and soleus muscles in anae sthetized, ventilated rats during monitoring of evoked twitch response to indirect (nerve) train-of-four stimulation. Results: The ED50 and ED95 of succinylcholine in control rats were (mean +/- SD) 204 +/- 41 and 382 +/- 96 mu g.kg(-1), respectively, in the tibialis muscle, and 280 +/- 52 and 629 +/- 168 mu g.kg(-1) in the soleus muscle (P < 0.05 between muscles). In the acute and chronic tacrine groups, the mean ED 50 and ED95 ranged from 166-197 and 277-396 mu g.kg-1, respectively, i n the tibialis muscle, and 248-333 and 546-667 mu g.kg(-1), in the sol eus muscle. Dose responses did not differ among acute and chronic tacr ine groups and the control group. Conclusion: Chronic oral tacrine doe s not alter muscle response to succinylcholine in the rat. This may no t apply to Alzheimer patients receiving chronic tacrine since the inte raction between acute tacrine and succinylcholine in the rat differs f rom that in humans.