Tacrine does not alter the potency of succinylcholine in the rat

Purpose

Tacrine is a cholinesterase inhibitor used to manage Alzheimer’s dementia. Giveniv, it prolongs succinylcholine blockade in humans but the effects of chronic oral tacrine are not known.

Methods

Groups 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 tacrineiv. Twelve to 18 hr after the last gavage of tacrine or saline, and ~20 min afteriv tacrine, cumulative dose-response curves of succinylcholine were determined in the tibialis and soleus muscles in anaesthetized, 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 μg · kg^?1 respectively, in the tibialis muscle, and 280 ± 52 and 629 ± 168 μg · kg^?1 in the soleus muscle (P < 0.05 between muscles). In the acute and chronic tacrine groups, the mean ED₅₀ and ED₉₅ ranged from 166–197 and 277–396 μg · kg^?1, respectively, in the tibialis muscle, and 248–333 and 546–667 μg · kg^?1, in the soleus muscle. Dose responses did not differ among acute and chronic tacrine groups and the control group.

Conclusion

Chronic oral tacrine does not alter muscle response to succinylcholine in the rat. This may not apply to Alzheimer patients receiving chronic tacrine since the interaction between acute tacrine and succinylcholine in the rat differs from that in humans.