Summary
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1.
The anticholinergic activity of amitriptyline and a new antidepressant, nortriptyline, which is a secondary amine related to amitriptyline, were compared on guinea pig ileum and salivation of dogs. Both are active anticholinergic agents, but somewhat atypical, by these tests. Amitriptyline caused suppression of salivation at lower doses than nortriptyline. On guinea pig ileum, amitriptyline was about twice as active as nortriptyline.
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2.
Both compounds decrease the tremor and salivation induced in mice by Tremorine. They differ from atropine in showing a greater effect on tremor than upon salivation.
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3.
Both amitriptyline and nortriptyline are effective in elevating the threshold dose of arecoline that produces desynchronization of the high voltage slow activity with spindles seen in the EEG of cats with lesions at the pontomesencephalic junction. They do not cause EEG behavioral dissociation like atropine.
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4.
It is suggested that although these compounds are effective in antagonizing the central effects of cholinergic agents, they are different in this regard from atropine and other tertiary amines that have been reported to cause hallucinations in patients.
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Rathbun, R.C., Slater, I.H. Amitriptyline and nortriptyline as antagonists of central and peripheral cholinergic activation. Psychopharmacologia 4, 114–125 (1963). https://doi.org/10.1007/BF00413329
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DOI: https://doi.org/10.1007/BF00413329