Opipramol

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Opipramol
Clinical data
Trade namesInsidon, Pramolan, others
Other namesG-33040; RP-8307[1]
AHFS/Drugs.comInternational Drug Names
Routes of
administration		Oral
ATC code
Legal status
Legal status
  • BR: Class C1 (Other controlled substances)[2]
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability94%[3]
Protein binding91%[3]
MetabolismCYP2D6-mediated[3]
Elimination half-life6–11 hours[3]
ExcretionUrine (70%), feces (10%)[3]
Identifiers
  • 4-[3-(5H-dibenz[b,f]azepin- 5-yl)propyl]-1-piperazinethanol
JSmol)
  • OCCN1CCN(CC1)CCCN4c2ccccc2\C=C/c3ccccc34
  • InChI=1S/C23H29N3O/c27-19-18-25-16-14-24(15-17-25)12-5-13-26-22-8-3-1-6-20(22)10-11-21-7-2-4-9-23(21)26/h1-4,6-11,27H,5,12-19H2 checkY
  • Key:YNZFUWZUGRBMHL-UHFFFAOYSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Opipramol, sold under the brand name Insidon among others, is an

SIGMAR1 agonist.[7] It was developed by Schindler and Blattner in 1961.[8]

Medical uses

Opipramol is typically used in the treatment of

somatoform disorders.[3][6] Preliminary studies suggest that opipramol shows potential clinical significance in the treatment of severe sleep bruxism.[9]

Contraindications

Pregnancy and lactation

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.

Side effects

Frequently (≥1% to <10%) reported adverse reactions with opipramol, especially at the beginning of the treatment, include

dry mouth, blocked nose, hypotension
, and orthostatic dysregulation.

Adverse reactions reported occasionally (≥0.1% to <1%) include

palpitations.[11][12][13][3]

Rarely (≥0.01% to <0.1%) reported adverse reactions include excitation, headache,

sweating, sleep disturbances, edema, galactorrhea, urine blockage, nausea and vomiting, fever,[14] 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.[3]

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.[13][3][15]

It could also cause headache.

Overdose

Main article: Tricyclic antidepressant overdose

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.

Since no

artificial respiration. Convulsions should be managed with anticonvulsants (typically diazepam), while monitoring for any worsening in CNS depression. Hypotension can be treated by assuming the corresponding recovery position, by increasing plasma volume with saline infusions, or by pressors, such as adrenaline or dobutamine
.

Interactions

Opipramol can be co-prescribed with other psychiatric drugs, such as antidepressants, anxiolytics and antipsychotics, in which case it can interact with them. Most problematic interactions are generally additive or synergistic, such that, when drugs are combined, their effects intensify, which usually manifests as an increase in side effects, but can also be dangerous, depending on the drugs involved.

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 TCAs, 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, on the other hand, can reduce the plasma concentration of opipramol and thereby weaken its therapeutic effect.[3]

Pharmacology

Pharmacodynamics

See also: Pharmacology of antidepressants and Tricyclic antidepressant § Binding profiles
Opipramol[16]
Site Ki (nM) Species Ref
σ1 0.2–50 Rodent [17][18][19]
σ2 110 ND [20]
SERTTooltip Serotonin transporter ≥2,200 Rat/? [21][22][23]
NETTooltip Norepinephrine transporter ≥700 Rat/? [21][22][23]
DATTooltip Dopamine transporter ≥3,000 Rat/? [21][22][23]
5-HT1A >10,000 ? [23]
5-HT2A 120 ? [23]
5-HT2C ND ND ND
α1 200 ? [23]
α2 6,100 ? [23]
D1
 900 Rat [19]
D2
 120–300 Rat [23][19]
H1 6.03 Human [24]
H2 4,470 Human [24]
H3 61,700 Human [24]
H4 >100,000 Human [24]
mAChTooltip Muscarinic acetylcholine receptor 3,300 ? [23]
NMDA/PCP >30,000 Rat [19]
Values are Ki (nM). The smaller the value, the more strongly the drug binds to the site.

Opipramol acts as a high

equipotent with.[17] The sigma receptor agonism of opipramol is thought to be responsible for its therapeutic benefits against anxiety and depression.[7][3]

Unlike other TCAs, opipramol does not

D2, serotonin 5-HT2, and α1-adrenergic receptors.[3][23] H1 receptor antagonism accounts for its antihistamine effects and associated sedative side effects.[6][3] In contrast to other TCAs, opipramol has very low affinity for the muscarinic acetylcholine receptors and virtually no anticholinergic effects.[23][25]

Sigma receptors are a set of

downregulated but σ1 receptors are not.[3]

Pharmacokinetics

Opipramol is rapidly and completely

terminal half-life in plasma is 6–11 hours.[3] About 70% is eliminated in urine with 10% unaltered.[3] The remaining portion is eliminated through feces.[3]

History

Opipramol was developed by

Geigy.[27] It first appeared in the literature in 1952 and was patented in 1961.[27] The drug was first introduced for use in medicine in 1961.[27] Opipramol was one of the first TCAs to be introduced, with imipramine marketed in the 1950s and amitriptyline marketed in 1961.[27]

Society and culture

Opipramol as Insidon and Pramolan 50 mg tablets.

Generic names

Opipramol is the

Latin is opipramolum.[4][5]

Brand names

Opipramol is marketed under the brand names Deprenil, Dinsidon, Ensidon, Insidon, Insomin, Inzeton, Nisidana, Opipram, Opramol, Oprimol, Pramolan, and Sympramol among others.[1][4][5]

References

  1. ^
    ISBN 978-1-4757-2085-3
    .
  2. ^ Anvisa (2023-03-31). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 2023-04-04). Archived from the original on 2023-08-03. Retrieved 2023-08-16.
  3. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac ad ae Mohapatra S, Rath NM, Agrawal A, Verma J (October 2013). "Opipramol: A Novel Drug" (PDF). Delhi Psychiatry Journal. 16 (2): 409–411. Archived from the original (PDF) on 2020-07-11. Retrieved 2014-03-25.
  4. ^
    ISBN 978-3-88763-075-1
    .
  5. ^ a b c d "Opipramol".
  6. ^
    S2CID 27014778
    .
  7. ^
    S2CID 260238755
    .
  8. S2CID 40241272
    .
  9. PMID 33499332
    .
  10. PMID 32151075
    .
  11. S2CID 74130809
    .
  12. S2CID 39368370
    .
  13. ^
    PMID 28320023
    .
  14. PMID 26417811
    . Retrieved 2 April 2022.
  15. S2CID 260242120
    .
  16. ^ Roth BL, Driscol J. "PDSP Ki Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved 14 August 2017.
  17. ^
    PMID 8755605
    .
  18. PMID 2477524
    .
  19. ^
    S2CID 23110359
    .
  20. PMID 2568580
    .
  21. ^
    S2CID 36424574
    .
  22. ^
    ISBN 978-0-89603-121-0
    .
  23. ^
    S2CID 5832198
    .
  24. ^
    S2CID 14274150
    .
  25. ISBN 978-1-118-18552-0
    .
  26. S2CID 24448788
    .
  27. ^
    PMID 19557250
    .
  28. ISBN 978-94-011-4439-1
    .