Tacrine does not alter the potency of succinylcholine in the rat.
OBJECTIVE
Tacrine is a cholinesterase inhibitor used to manage Alzheimer's dementia. Given iv, 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 l 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 -20 min after iv 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 micrograms.kg-1, respectively in the tibialis muscle, and 280 +/- 52 and 629 +/- 168 micrograms.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 micrograms.kg-1., respectively, in the tibialis muscle, and 248-333 and 546-667 micrograms.kg-1, in the soleus muscle. Dose responses did not differ among acute and chronic tacrine groups and the control group.


CONCLUSIONS
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.
Ibebunjo
C
C
Department of Anaesthesia, Royal Victoria Hospital, Montréal, Québec, Canada.
Eshelby
D
D
Donati
F
F
Fox
G S
GS
Tchervenkov
J I
JI
D000284:Administration, Oral; D000544:Alzheimer Disease / Q000188:drug therapy; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000187:drug effects; D005260:Female; D006614:Hindlimb; D006801:Humans; D007275:Injections, Intravenous; D009119:Muscle Contraction / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects / Q000294:innervation; D019148:Neuromuscular Blockade; D009467:Neuromuscular Depolarizing Agents / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013390:Succinylcholine / Q000008:administration & dosage / Q000494:pharmacology*; D013619:Tacrine / Q000008:administration & dosage / Q000494:pharmacology*
D002800:Cholinesterase Inhibitors; D009467:Neuromuscular Depolarizing Agents; D013619:Tacrine; D013390:Succinylcholine