Non-anticholinesterase, non-cholinergic effect of tacrine on gastrointestinal smooth muscle tissues of rat.
BACKGROUND
Tacrine is a cholinesterase inhibitor used for the treatment of Alzheimer's disease. The drug also has an effect on a number of tissues and organs that are not targets of its therapeutical action in this disease. The gastrointestinal tract is one such affected organ.


OBJECTIVE
To investigate the in vitro effects of tacrine on rat stomach smooth muscles and determine the correlation between the anticholinesterase activity of the drug and the provoked smooth muscle mechanical responses.


METHODS
The acetylcholinesterase activity was determined spectrophotometrically in tissue homogenates by the Ellman's method. Spectrophotometer "Cary 1" was used. The contraction activity of smooth muscle strips (11-12 mm long and 1.5-2 mm wide) from the gastric corpus was measured isometrically with Microtechna (Czech Republic) amplifier and recorded by Linseis (Germany) recorder.


RESULTS
The results showed significant increase in the tacrine-induced contractions concurrent with reduction of the acetylcholinesterase activity within the concentration range of 10(-7)-10(-5) mol/l. The tendencies of development of both processes showed a high level of correlation (>0.99). Tacrine-induced contractions were inhibited significantly with atropine, ipatropium and hexametonium. They had a cholinergic character and most likely were due to endogenous acetylcholine accumulated as a result of inhibition of cholinesterase activity. An opposite tendency (correlation = - 0.98) was observed at tacrine concentrations of > or = 5.10(-5) mol/l: the decrease in the enzyme activity coincided with relaxation of muscle preparations.


CONCLUSIONS
The analysis of the results suggests that the observed relaxation is non-anticholinesterase and non-cholinergic.
Department of Medical Physics, Medical University-Plovdiv, Bulgaria.
Valentin I
VI
Turiiski
Mariana D
MD
Argirova
Atanas D
AD
Krustev
D000704:Analysis of Variance; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D041981:Gastrointestinal Tract / Q000187:drug effects*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013619:Tacrine / Q000494:pharmacology*
D002800:Cholinesterase Inhibitors; D013619:Tacrine