opipramol

Opipramol is typically used in the treatment of generalized anxiety disorder (GAD) and somatoform disorders. Preliminary studies suggest that opipramol shows potential clinical significance in the treatment of severe sleep bruxism.{{cite journal | vauthors = Wieckiewicz M, Martynowicz H, Wieczorek T, Wojakowska A, Sluzalec-Wieckiewicz K, Gac P, Poreba R, Mazur G, Winocur E, Smardz J | display-authors = 6 | title = Consecutive Controlled Case Series on Effectiveness of Opipramol in Severe Sleep Bruxism Management-Preliminary Study on New Therapeutic Path | journal = Brain Sciences | volume = 11 | issue = 2 | pages = 146 | date = January 2021 | pmid = 33499332 | pmc = 7911172 | doi = 10.3390/brainsci11020146 | doi-access = free }}

• In patients with hypersensitivity to opipramol or another component of the formulation
• Acute alcohol, sedative, analgesic, and antidepressant intoxications
• Acute urinary retention
• Acute delirium
• Untreated narrow-angle glaucoma
• Benign prostatic hyperplasia with residual urinary retention
• Paralytic ileus
• Pre-existing higher-grade atrioventricular blockages or diffuse supraventricular or ventricular stimulus conduction disturbances
• Combination with monoamine oxidase inhibitor (MAOI)

Experimental animal studies did not indicate injurious effects of opipramol on the embryonic development or fertility. Opipramol should only be prescribed during pregnancy, particularly in the first trimester, for compelling indication.

It should not be used during lactation and breastfeeding, since it passes into breast milk in small quantities.

Frequently (≥1% to <10%) reported adverse reactions with opipramol, especially at the beginning of the treatment, include fatigue, dry mouth, blocked nose, hypotension, and orthostatic dysregulation.

Adverse reactions reported occasionally (≥0.1% to <1%) include dizziness, stupor, micturition disturbances, vigilance, accommodation disturbances, tremor, weight gain,{{cite journal | vauthors = Carpéné C, Les F, Mercader J, Gomez-Zorita S, Grolleau JL, Boulet N, Fontaine J, Iglesias-Osma MC, Garcia-Barrado MJ | display-authors = 6 | title = Opipramol Inhibits Lipolysis in Human Adipocytes without Altering Glucose Uptake and Differently from Antipsychotic and Antidepressant Drugs with Adverse Effects on Body Weight Control | journal = Pharmaceuticals | volume = 13 | issue = 3 | pages = 41 | date = March 2020 | pmid = 32151075 | pmc = 7151722 | doi = 10.3390/ph13030041 | doi-access = free }} thirst, allergic skin reactions (rash, urticaria), abnormal ejaculation, erectile impotence, constipation, transient increases in liver enzymes, tachycardia, and palpitations.{{Cite journal | vauthors = Jepson K, Beaumont G |date=March 1973 |title=A Comparative Trial of Opipramol and Chlordiazepoxide in the Treatment of Anxiety |url=https://journals.sagepub.com/doi/abs/10.1177/030006057300100301 |journal=Journal of International Medical Research |volume=1 |issue=3 |pages=145–150 |doi=10.1177/030006057300100301 |s2cid=74130809 |issn=0300-0605|url-access=subscription }}{{cite journal | vauthors = Volz HP, Möller HJ, Reimann I, Stoll KD | title = Opipramol for the treatment of somatoform disorders results from a placebo-controlled trial | journal = European Neuropsychopharmacology | volume = 10 | issue = 3 | pages = 211–217 | date = May 2000 | pmid = 10793324 | doi = 10.1016/S0924-977X(00)00074-2 | s2cid = 39368370 }}{{cite journal | vauthors = Gahr M, Hiemke C, Connemann BJ | title = [Update Opipramol] | language = de | journal = Fortschritte der Neurologie-Psychiatrie | volume = 85 | issue = 3 | pages = 139–145 | date = March 2017 | pmid = 28320023 | doi = 10.1055/s-0043-100762 }}

Rarely (≥0.01% to <0.1%) reported adverse reactions include excitation, headache, paresthesia especially in elderly patients, restlessness, sweating, sleep disturbances, edema, galactorrhea, urine blockage, nausea and vomiting, fever,{{cite journal | vauthors = Krysta K, Murawiec S, Warchala A, Zawada K, Cubała WJ, Wiglusz MS, Jakuszkowiak-Wojten K, Krzystanek M, Krupka-Matuszczyk I | display-authors = 6 | title = Modern indications for the use of opipramol | journal = Psychiatria Danubina | volume = 27 | issue = Suppl 1 | pages = S435–S437 | date = September 2015 | pmid = 26417811 | url = https://hrcak.srce.hr/file/384203 | access-date = 2 April 2022 }} collapse conditions, stimulation conducting disturbances, intensification of present heart insufficiency, blood profile changes particularly leukopenia, confusion, delirium, stomach complaints, taste disturbance, and paralytic ileus especially with sudden discontinuation of a longer-term high-dose therapy.

Very rarely (<0.01%) reported adverse reactions include seizures, motor disorders (akathisia, dyskinesia, ataxia), polyneuropathy, glaucoma, anxiety, hair loss, agranulocytosis, severe liver dysfunction after long-term treatment, jaundice, and chronic liver damage.{{cite journal | vauthors = Braun JS, Geiger R, Wehner H, Schäffer S, Berger M | title = Hepatitis caused by antidepressive therapy with maprotiline and opipramol | journal = Pharmacopsychiatry | volume = 31 | issue = 4 | pages = 152–155 | date = July 1998 | pmid = 9754852 | doi = 10.1055/s-2007-979319 | s2cid = 260242120 }}

{{Main|Tricyclic antidepressant overdose}}{{Section needs more citations|date=February 2025}}

Symptoms of intoxication from overdose include drowsiness, insomnia, stupor, agitation, coma, transient confusion, increased anxiety, ataxia, convulsions, oliguria, anuria, tachycardia or bradycardia, arrhythmia, AV block, hypotension, shock, respiratory depression, and, rarely, cardiac arrest.

While opipramol is not a monoamine reuptake inhibitor, any irreversible MAOIs should still be discontinued at least 14 days before treatment. Opipramol can compete with other tricyclic antidepressants, beta blockers, antiarrhythmics (of class 1c), and other drugs for microsomal enzymes, which can lead to slower metabolism and higher plasma concentrations of these drugs. Co-administration of antipsychotics (e.g., haloperidol, risperidone) can increase the plasma concentration of opipramol. Barbiturates and anticonvulsants can reduce the plasma concentration of opipramol and thereby weaken its therapeutic effect.

{{See also|Pharmacology of antidepressants|Tricyclic antidepressant#Binding profiles}}

Opipramol acts as a high affinity sigma receptor agonist, primarily of the σ₁ subtype, but also of the σ₂ subtype with lower affinity.{{cite journal|vauthors=Mohapatra S, Rath NM, Agrawal A, Verma J|title=Opipramol: A Novel Drug|journal=Delhi Psychiatry Journal|date=October 2013|volume=16|issue=2|pages=409–411|url=http://medind.nic.in/daa/t13/i2/daat13i2p409.pdf|access-date=2014-03-25|archive-date=2020-07-11|archive-url=https://web.archive.org/web/20200711034539/http://medind.nic.in/daa/t13/i2/daat13i2p409.pdf|url-status=dead}} In one study of σ₁ receptor ligands that also included haloperidol, pentazocine, (+)-3-PPP, ditolylguanidine, dextromethorphan, SKF-10,047 ((±)-alazocine), ifenprodil, progesterone, and others, opipramol showed the highest affinity (K_i = 0.2–0.3) for the guinea pig σ₁ receptor of all the tested ligands except haloperidol, which it was approximately equipotent with. The sigma receptor agonism of opipramol is thought to be responsible for its therapeutic benefits against anxiety and depression.

Unlike other TCAs, opipramol does not inhibit the reuptake of serotonin or norepinephrine. However, it does act as a high affinity antagonist of the histamine H₁ receptor and is a low to moderate affinity antagonist of the dopamine D₂, serotonin 5-HT₂, and α₁-adrenergic receptors. H₁ receptor antagonism accounts for its antihistamine effects and associated sedative side effects. In contrast to other TCAs, opipramol has very low affinity for the muscarinic acetylcholine receptors and virtually no anticholinergic effects.{{cite book| vauthors = Botana LM, Loza M |title=Therapeutic Targets: Modulation, Inhibition, and Activation|url=https://books.google.com/books?id=3XJ8PXFCXq4C&pg=PA251|date=20 April 2012|publisher=John Wiley & Sons|isbn=978-1-118-18552-0|pages=251–}}

Sigma receptors are a set of proteins located in the endoplasmic reticulum. σ₁ receptors play key role in potentiating intracellular calcium mobilization thereby acting as sensor or modulator of calcium signaling. Occupancy of σ₁ receptors by agonists causes translocation of the receptor from endoplasmic reticulum to peripheral areas (membranes) where the σ₁ receptors cause neurotransmitter release. Opipramol is said to have a biphasic action, with prompt initial improvement of tension, anxiety, and insomnia followed by improved mood later. Hence, it is an anxiolytic with an antidepressant component. After sub-chronic treatment with opipramol, σ₂ receptors are significantly downregulated but σ₁ receptors are not.

Opipramol is rapidly and completely absorbed by the gastrointestinal tract. The bioavailability of opipramol amounts to 94%. After single oral administration of 50 mg, the peak plasma concentration of the drug is reached after 3.3 hours and amounts to 15.6 ng/mL. After single oral administration of 100 mg the maximum plasma concentration is reached after 3 hours and amounts to 33.2 ng/mL. Therapeutic concentrations of opipramol range from 140 to 550 nmol/L.{{cite journal | vauthors = Gutteck U, Rentsch KM | title = Therapeutic drug monitoring of 13 antidepressant and five neuroleptic drugs in serum with liquid chromatography-electrospray ionization mass spectrometry | journal = Clinical Chemistry and Laboratory Medicine | volume = 41 | issue = 12 | pages = 1571–1579 | date = December 2003 | pmid = 14708881 | doi = 10.1515/CCLM.2003.240 | s2cid = 24448788 }} The plasma protein binding amounts to approximately 91% and the volume of distribution is approximately 10 L/kg. Opipramol is partially metabolized in the liver to deshydroxyethylopipramol. Metabolism occurs through the CYP2D6 isoenzyme. Its terminal half-life in plasma is 6–11 hours. About 70% is eliminated in urine with 10% unaltered. The remaining portion is eliminated through feces.

Opipramol was developed by Geigy.{{cite journal | vauthors = Andersen J, Kristensen AS, Bang-Andersen B, Strømgaard K | title = Recent advances in the understanding of the interaction of antidepressant drugs with serotonin and norepinephrine transporters | journal = Chemical Communications | issue = 25 | pages = 3677–3692 | date = July 2009 | pmid = 19557250 | doi = 10.1039/b903035m }} It first appeared in the literature in 1952 and was patented in 1961. The drug was first introduced for use in medicine in 1961. Opipramol was one of the first TCAs to be introduced, with imipramine marketed in the 1950s and amitriptyline marketed in 1961.

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Opipramol is the English, German, French, and Spanish generic name of the drug and its {{abbrlink|INN|International Nonproprietary Name}}, {{abbrlink|BAN|British Approved Name}}, and {{abbrlink|DCF|Dénomination Commune Française}}, while opipramol hydrochloride is its {{abbrlink|USAN|United States Adopted Name}}, {{abbrlink|BANM|British Approved Name}}, and {{abbrlink|JAN|Japanese Accepted Name}}.{{cite book| vauthors = Elks J |title=The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies|url=https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA904|date=14 November 2014|publisher=Springer|isbn=978-1-4757-2085-3|pages=904–}}{{cite book|title=Index Nominum 2000: International Drug Directory|url=https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA760|year=2000|publisher=Taylor & Francis|isbn=978-3-88763-075-1|pages=760–761}}{{cite book| vauthors = Morton IK, Hall JM |title=Concise Dictionary of Pharmacological Agents: Properties and Synonyms|url=https://books.google.com/books?id=tsjrCAAAQBAJ&pg=PA209|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-94-011-4439-1|pages=209–}}{{Cite web | url=https://www.drugs.com/international/opipramol.html |title = Opipramol}} Its generic name in Italian and its {{abbrlink|DCIT|Denominazione Comune Italiana}} is opipramolo and in Latin is opipramolum.

Opipramol is marketed under the brand names Deprenil, Dinsidon, Ensidon, Insidon, Insomin, Inzeton, Nisidana, Opipram, Opramol, Oprimol, Pramolan, and Sympramol among others.

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{{Tricyclics}}

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