Freeman_1988_Eur.J.Pharmacol_154_59

The centrally acting anticholinesterase drug tacrine has been shown to block K+ channels in guinea pig left atrium. It competitively blocks the negative inotropic effects of adenosine, 2-chloroadenosine and carbachol. Ka values obtained from dose ratio plots were 2.5, 3.5 and 2.9 microM respectively. It was also able to antagonize the shortening of the action potential due to these compounds. Doses of tacrine ranging from 1 to 4 microM restored the AP configuration close to control values. Tacrine also antagonized the binding of 1-quinuclidinyl[phenyl-4-3H]benzilate ([3H]QNB) to membranes derived from the atrium and cerebral cortex. Ki values of 1.8 +/- 0.33 and 1.3 +/- 0.47 microM were obtained respectively. Tacrine was a weak competitor of [3H]phenylisopropyladenosine ([3H]L-PIA) binding in brain membranes. Its diverse pharmacological effects may be relevant to its use in Alzheimer's disease.