Iprindole

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Iprindole
Clinical data
Trade namesProndol, Galatur, Tertran
Other namesPramindole; WY-3263
Routes of
administration		Oral
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
MetabolismHepatic[3]
Elimination half-life52.5 hours[1]
ExcretionUrine, Feces[2]
Identifiers
  • 3-(6,7,8,9,10,11-hexahydro-5H-cycloocta[b]indol-5-yl)-N,N-dimethylpropan-1-amine
JSmol)
  • c13c(n(c2ccccc12)CCCN(C)C)CCCCCC3
  • InChI=1S/C19H28N2/c1-20(2)14-9-15-21-18-12-6-4-3-5-10-16(18)17-11-7-8-13-19(17)21/h7-8,11,13H,3-6,9-10,12,14-15H2,1-2H3 checkY
  • Key:PLIGPBGDXASWPX-UHFFFAOYSA-N checkY
  (verify)

Iprindole, sold under the brand names Prondol, Galatur, and Tertran, is an atypical tricyclic antidepressant (TCA) that has been used in the United Kingdom and Ireland for the treatment of depression but appears to no longer be marketed.[4][5][6][7] It was developed by Wyeth and was marketed in 1967.[8] The drug has been described by some as the first "second-generation" antidepressant to be introduced.[9] However, it was very little-used compared to other TCAs, with the number of prescriptions dispensed only in the thousands.[10]

Medical uses

Iprindole was used in the treatment of major depressive disorder in dosages similar to those of other TCAs.[5][11]

Contraindications

Iprindole has been associated with

alcoholics or people with pre-existing liver disease.[8][12][13][14]
If such symptoms are encountered iprindole should be discontinued immediately.

Side effects

dry mouth and constipation are either greatly reduced in comparison to imipramine and most other TCAs or fully lacking with iprindole.[15] However, it still has significant antihistamine effects and therefore can produce sedation, though this is diminished relative to other TCAs similarly.[16] Iprindole also lacks significant alpha-blocking properties, and hence does not pose a risk of orthostatic hypotension.[16]

Overdose

Main article: Tricyclic antidepressant overdose

In

toxic than most other TCAs and is considered relatively benign.[17] For instance, between 1974 and 1985, only two deaths associated with iprindole were recorded in the United Kingdom, whereas 278 were reported for imipramine, although imipramine is used far more often than iprindole.[10][17]

Interactions

Iprindole has been shown to be a potent

octopamine, amphetamine, methamphetamine, fenfluramine, phenelzine, tranylcypromine, trimipramine, and fluoxetine, likely via inactivating cytochrome P450 enzymes.[3][18][19][20][21][22] It also inhibits its own metabolism.[21]

On account of these

terminal half-lives by 2- to 3-fold, strongly augmenting both their physiological effects and neurotoxicity in the process.[23][24][25]

Pharmacology

Pharmacodynamics

See also: Pharmacology of antidepressants and Tricyclic antidepressant § Binding profiles
Iprindole[26]
Site Ki (nM) Species Ref
SERTTooltip Serotonin transporter 1,620–3,300 Human [27][28]
NETTooltip Norepinephrine transporter 1,262 Human [27]
DATTooltip Dopamine transporter 6,530 Human [27]
5-HT1A 2,800 Human [28]
5-HT2A 217–280 Human/rat [28][29]
5-HT2C 206 Rat [29]
α1 2,300 Human [30]
α2 8,600 Human [30]
β
 >10,000 Mammal [31][32]
D2
 6,300 Rat [32]
H1 100–130 Human/rat [30][33]
H2 200–8,300 Guinea pig [32][34][35]
mAChTooltip Muscarinic acetylcholine receptor 2,100 Human [30][36]
σ1 >10,000 Rat [37]
Values are Ki (nM). The smaller the value, the more strongly the drug binds to the site.

Iprindole is unique compared to most other TCAs in that it is a very weak and negligible

animal research, the antidepressant effects of iprindole may be mediated through downstream dopaminergic mechanisms.[41]

The

binding affinities of iprindole for various biological targets are presented in the table to the right.[26] It is presumed to act as an inhibitor or antagonist/inverse agonist of all sites. Considering the range of its therapeutic concentrations (e.g., 63–271 nM at 90 mg/day),[1] only the actions of iprindole on the 5-HT2 and histamine receptors might be anticipated to be of possible clinical significance.[1] However, it is unknown whether these actions are in fact responsible for the antidepressant effects of iprindole. The plasma protein binding
of iprindole and hence its free percentage and potentially bioactive concentrations do not seem to be known.

Pharmacokinetics

Only one study appears to have evaluated the

steady-state concentrations should be reached by 99% within 15 to 20 days of treatment.[1]

Chemistry

Iprindole is a

molecular weight of 284.439 g/mol.[47] The drug has been used commercially as both the free base and the hydrochloride salt.[47] The CAS Registry Number of the free base is 5560-72-5 and of the hydrochloride is 20432-64-8.[47]

History

Iprindole was developed by Wyeth and was marketed in 1967.[8][48]

Society and culture

Generic names

Iprindole is the

Latin is iprindolum.[4] Iprindole was originally known unofficially as pramindole.[47][4]

Brand names

Iprindole has been marketed under the brand name Prondol by Wyeth in the United Kingdom and Ireland for the indication of major depressive disorder,[50] and has also been sold as Galatur and Tertran by Wyeth.[47]

Availability

Iprindole was previously available in the United Kingdom and Ireland[50] but seems to no longer be available for medical use in any country.[4]

References

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  8. ^
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  26. ^ a b 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 7 May 2022.
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  28. ^
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  29. ^
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  44. S2CID 4181062
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  46. ISBN 978-0-19-162675-3
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  50. ^
    ISBN 978-0-85369-840-1
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Further reading
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