Assessment of the anticholinergic effects of antidepressants in a single-dose cross-over study of salivation and plasma levels

  title={Assessment of the anticholinergic effects of antidepressants in a single-dose cross-over study of salivation and plasma levels},
  author={Lars Clemmesen and P. L. Mikkelsen and H Lund and Tom Gert Bolwig and Ole J. Rafaelsen},
In order to evaluate the anticholinergic effect of antidepressant drugs, 11 healthy volunteers were given single oral doses of reference drug, test drugs or placebo on a double-blind basis at weekly intervals. The doses corresponded to average daily patient medications. Spontaneous whole mouth and parotid salivation, and plasma levels of drug and possible metabolites were measured 2, 6 and 10h after drug administration.Moderate, statistically significant inhibition of salivation was found when… 

Effects of chronic amitriptyline administration on saliva from the parotid and submandibular glands of the rat

Protein concentration and amylase activity of nerve-elicited parotid saliva were, however, greatly increased by chronic amitriptyline administration, and possible mechanisms include changes in cholinergic receptor binding, release of neuropeptides and variations in phosphatidylinositol turnover.

Cholinergic dysfunction of heart, pupil, salivary glands, and urinary bladder in healthy volunteers during long-term treatment with clomipramine

It is suggested that the easy obtainable function test of HRV at standing can be used as an estimate of over-all cholinergic dysfunction during treatment with tricyclic antidepressants.

Pharmaceutical treatment for cognitive deficits in Alzheimer’s disease and other neurodegenerative conditions: exploring new territory using traditional tools and established maps

This research provided first evidence of the following: aged primates can be used as ‘models’ for human age-related neurodegenerative diseases; key cognitive deficits in early AD share important conceptual similarities to deficits in both aged monkeys as well as non-demented humans; and that many other classes of drugs would not likely succeed.



The Peripheral Anticholinergic Activity of Tricyclic Antidepressants: Comparison of Amitriptyline and Desipramine in Human Volunteers

Pupil diameter was not affected by amitriptyline, whereas desipramine caused mydriasis, indicating that pupil size is not a reliable measure of anticholinergic activity in the case of drugs which also affect adrenergic mechanisms.

A comparison of the pharmacodynamic profiles of nomifensine and amitriptyline in normal subjects.

Nomifensine treatment did not influence salivary flow and did not significantly affect psychomotor performance, but amitriptyline treatment significantly reduced salivaries flow and was associated with significant sedation and reduced concentration, and both significantly inhibited DA uptake and 5-HT uptake.

Changes in saliva secretion and accommodation width during short-term administration of imipramine and zimelidine in healthy volunteers.

The full therapeutic dose of the new compound zimelidine could be given in one single dose in the morning without causing more pronounced anti-cholinergic effects than the reference compound imipramine which was given at 25-mg doses three times daily.

Anticholinergic and blood pressure effects of mianserin, amitriptyline and placebo.

  • H. Kopera
  • Psychology, Medicine
    British journal of clinical pharmacology
  • 1978
Mianserin in doses of up to 60 mg daily given to healthy males seemed to lack the anticholinergic effects and postural hypotension associated with amitriptyline treatment.

Pharmacokinetics of desmethylimipramine and nortriptyline in man after single and multiple oral doses — A cross-over study

  • B. Alexanderson
  • Biology, Medicine
    European Journal of Clinical Pharmacology
  • 2004
The study shows that the “steady-state” plasma level of DMI, like that of NT, can be predicted accurately from single-dose plasma-level data, and if the kinetic characteristics of one of these drugs in a subject are known, it is possible to predict the plasma kinetics of the other compound.

Saliva secretion following long-term antidepressant treatment with nortriptyline controlled by plasma levels.

The results confirmed that long-term treatment with nortriptyline is followed by hyposecretion or xerostomia and the changes in salivary secretion are useful as an indicator of side effects.

Comparison of single dose kinetics of imipramine, nortriptyline and antipyrine in man

The data indicate that inter- and intraindividual variations in hepatic blood flow may influence the measurements, and possible sources of variability are individual differences in hepatics extraction kinetics, and differences in binding to blood constitutents.

Pharmacodynamic studies on mianserin and its interaction with clonidine

It is demonstrated that mianserin does not significantly interfere with the responses to a single oral dose of clonidine, and there was no evidence that mianerserin interfered with the ability ofClonidine to diminish salivary flow, cause sedation, and reduce catecholamine output.

Autonomic actions and interactions of mianserin hydrochloride (Org. GB 94) and amitriptyline in patients with depressive illness

Mianserin hydrochloride appears to be free of anticholinergic effects as assessed by the measurement of salivary volume, pupil diameter and the interactions with guanethidine and thymoxamine on the pupil.