Depression Associated with Cimetidine

Rf, Billings; Tang, Shijie; Vm, Rakoff

doi:10.1177/070674378102600412

Cited by 21 publications

(5 citation statements)

References 6 publications

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“…In contrast, several cases of depression induced by cimetidine were reported (Johnson and Bailey 1979;Crowder and Pate 1980;Billings et al 1981;Pierce 1983). Billings et al (1981) suggested an imbalance between H 1 R and H 2 R signaling by the inhibition of the latter receptor, but disregards that several antidepressants are also moderately potent H 2 R antagonists. Antell et al (1989), however, negated any association of depression and cimetidine.…”

Section: Structure-activity Relationships For Antidepressants and Antmentioning

confidence: 91%

Interactions of recombinant human histamine H1, H2, H3, and H4 receptors with 34 antidepressants and antipsychotics

Appl

Holzammer

Dove

et al. 2011

Naunyn-Schmiedeberg's Arch Pharmacol

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Antidepressants and antipsychotics affect multiple molecular targets. Consequently, these drugs exhibit not only unique profiles of therapeutic effects but also several undesired effects. Histamine receptors (H₁R, H₂R, H₃R, and H₄R) belong to the large family of G protein-coupled receptors and are very important drug targets. All four H(x)R subtypes are expressed in the CNS. Interactions of lipophilic, blood-brain barrier-penetrating drugs with H(x)Rs could contribute to therapeutic and unwanted effects. Therefore, we investigated potencies H(x)R as well as potencies and (inverse) agonistic efficacies of 34 antidepressants and antipsychotics at HxRs in functional assays. We expressed human H(x)Rs in Sf9 insect cells and conducted radioligand competition binding experiments and functional steady-state GTPase assays. Ligand affinities and potencies were compared with literature data and related to therapeutic reference ranges. Almost all antidepressants and antipsychotics displayed high binding affinities to H₁R and behaved as antagonists. The atypical antidepressant trimipramine behaved as a high-affinity/high-potency H₂R antagonist (pK(i), 7.39; pK(B), 7.36; pA₂, 7.55). Docking to an H₂R model suggested a probable binding mode. The affinity of antidepressants and antipsychotics for H₃R was low. The atypical antipsychotic clozapine, known to induce agranulocytosis, exhibited partial H₄R agonism for which docking experiments provided a molecular basis. Clozapine also exhibited H₂R antagonism. We observed dissociations between pK(i) and pK (B) values as well as between pK(i) and pIC₅₀ values for H(x)Rs. Antidepressants and antipsychotics interact differentially with H(x)Rs. The concept of functional selectivity (also referred to as ligand-specific receptor conformations or biased signaling) explains dissociations between pK(i) and pK(B) values as well as differences between pK(i) and pIC₅₀ values. The H₁R antagonism of numerous antidepressants and antipsychotics is very pronounced. The H₂R antagonism of trimipramine and partial H₄R agonism of clozapine may be clinically relevant. We also discuss the possible role of the H₂R antagonism of clozapine for neutropenia/agranulocytosis induced by this compound. Finally, we discuss the methodological, conceptual, and clinical limitations of our study.

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Section: Structure-activity Relationships For Antidepressants and Antmentioning

confidence: 91%

Interactions of recombinant human histamine H1, H2, H3, and H4 receptors with 34 antidepressants and antipsychotics

Appl

Holzammer

Dove

et al. 2011

Naunyn-Schmiedeberg's Arch Pharmacol

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show abstract

“…It must be emphasized that the experience with cimetidine revealed that, where mental confusion occurred, the patients were generally elderly and had coexistent renal and/or hepatic impairment. The cases of depression, however, which have been linked to cimetidine tended to occur in younger and healthier patients (Johnson and Bailey, 1979;Crowder and Pate, 1980;Billings et al, 1981).…”

Section: Discussionmentioning

confidence: 99%

“…Cimetidine is a known cause of mental confusion, especially in the elderly and in those with renal and/or hepatic impairment (Russell and Lopez, 1980). Furthermore, cimetidine has been associated with depression (Johnson and Bailey, 1979;Crowder and Pate, 1980;Billings, Tang and Rakoff, 1981), even in physically healthy younger patients.…”

Section: Introductionmentioning

confidence: 99%

Effect of the H2-receptor antagonist ranitidine on depression and anxiety in duodenal ulcer patients

Robins¹,

Lucke²,

McFadyen³

et al. 1984

Postgraduate Medical Journal

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SummaryDepression and anxiety were measured during the course of a double-blind, placebo-controlled trial of the histamine H2-receptor antagonist, ranitidine (150 mg twice daily), in patients suffering from duodenal ulcer but free of systemic disease. There were 25 patients in the ranitidine group (mean age: 33-2 years) and 28 in the placebo group (mean age: 37-2 years). In both groups there was a highly significant and progressive decrease in depression and anxiety scores over the 4 weeks of treatment. There were no instances of mental confusion. In our group of otherwise physically healthy patients, ranitidine appeared to be free of neuropsychiatric complications.

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“…Similarly, the H 1 R antagonist terfenadine showed antidepressant-like activity in the olfactory bulbectomized model of depression [Song et al, 1996]. The H 2 R antagonist cimetidine showed depression-like activity in vulnerable patients and was suggested to be caused by an imbalance between H 1 R and H 2 R [Billings et al, 1981]. Indeed, this effect of cimetidine was also seen in animal models of depression and could be antagonized by co-administration of the H 1 R antagonist chlorpheniramine [O'Neill and Gertner, 1986].…”

Section: Role Of Histamine In Depressionmentioning

confidence: 97%

Histamine receptors as potential therapeutic targets to treat anxiety and depression

Raber

2005

Drug Development Research

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Increasing evidence supports a role for histamine in anxiety and depression. In most studies, histamine and stimulation of the histamine H 1 receptor (H 1 R) or blockade of the histamine H 2 receptor (H 2 R) increase measures of anxiety. In contrast, in most studies histamine reduces depression-like activity, which might be related to effects of histamine on waking. These effects of histamine on anxiety and depression make histamine receptor ligands attractive therapeutic targets. As most studies assessing the potential of histamine receptor ligands on depression did not exclude potential effects of these ligands on locomotor activity, more studies are warranted to determine the exact role of histamine receptor subtypes in depression. The effects of histamine-mediated signaling on anxiety and depression should also be considered in assessments of the potential of histamine H 3 receptor (H 3 R) ligands for conditions characterized by cognitive impairments as well as noncognitive behavioral impairments. Drug Dev. Res. 65:126-132, 2005.

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Depression Associated with Cimetidine

Cited by 21 publications

References 6 publications

Interactions of recombinant human histamine H1, H2, H3, and H4 receptors with 34 antidepressants and antipsychotics

Interactions of recombinant human histamine H1, H2, H3, and H4 receptors with 34 antidepressants and antipsychotics

Effect of the H2-receptor antagonist ranitidine on depression and anxiety in duodenal ulcer patients

Histamine receptors as potential therapeutic targets to treat anxiety and depression

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