Lofepramine, sold under the brand namesGamanil,Lomont, andTymelyt among others, is atricyclic antidepressant (TCA) which is used to treatdepression.[7][3][8] The TCAs are so named as they share the common property of having three rings in their chemical structure. Like most TCAs lofepramine is believed to work in relieving depression by increasing concentrations of the neurotransmittersnorepinephrine andserotonin in thesynapse, by inhibiting theirreuptake.[7] It is usually considered a third-generation TCA, as unlike the first- and second-generation TCAs it is relatively safe in overdose and has milder and less frequent side effects.[9]
Lofepramine use during pregnancy is advised against unless the benefits clearly outweigh the risks.[7] This is because its safety during pregnancy has not been established and animal studies have shown some potential for harm if used during pregnancy.[7] If used during the third trimester of pregnancy it can causeinsufficient breathing to meet oxygen requirements, agitation and withdrawal symptoms in the infant.[7] Likewise its use by breastfeeding women is advised against, except when the benefits clearly outweigh the risks, due to the fact it is excreted in the breast milk and may therefore adversely affect the infant.[7] Although the amount secreted in breast milk is likely too small to be harmful.[13]
Compared to other TCAs, lofepramine is considered to be less toxic in overdose.[13] Its treatment is mostly a matter of trying to reduce absorption of the drug, if possible, usinggastric lavage and monitoring for adverse effects on the heart.[7]
Monoamine oxidase inhibitors (MAOIs). Advised not to be started until at least 2 weeks after stopping MAOIs. MAOIs are advised not to be started until at least 1–2 weeks after stopping TCAs like lofepramine.
Moclobemide. Moclobemide is advised not to be started until at least one week after treatment with TCAs is discontinued.
Nitrates. Could possibly reduce the effects of sublingual tablets of nitrates (failure to dissolve under tongue owing to dry mouth).
Rifampicin. May accelerate lofepramine metabolism thereby decreasing plasma concentrations of lofepramine.
Ritonavir. May increase lofepramine concentration in the blood plasma.
Lofepramine is extensively metabolized, via cleavage of the p-chlorophenacyl group, to the TCA,desipramine, in humans.[7][8][1] However, it is unlikely this property plays a substantial role in its overall effects as lofepramine exhibits lowertoxicity andanticholinergicside effects relative to desipramine while retaining equivalent antidepressant efficacy.[8] The p-chlorophenacyl group is metabolized to p-chlorobenzoic acid which is then conjugated withglycine and excreted in the urine.[7] The desipramine metabolite is partly secreted in the faeces.[7] Other routes of metabolism includehydroxylation,glucuronidation,N-dealkylation andN-oxidation.[7][1]
Lofepramine was developed byLeo Läkemedel AB.[36] It first appeared in the literature in 1969 and was patented in 1970.[36] The drug was first introduced for the treatment of depression in either 1980 or 1983.[36][37]
Lofepramine is thegeneric name of the drug and itsINNTooltip International Nonproprietary Name andBANTooltip British Approved Name, whilelofepramine hydrochloride is itsUSANTooltip United States Adopted Name,BANMTooltip British Approved Name, andJANTooltip Japanese Accepted Name.[2][3][38][4] Its generic name inFrench and itsDCFTooltip Dénomination Commune Française arelofépramine, inSpanish andItalian and itsDCITTooltip Denominazione Comune Italiana arelofepramina, inGerman islofepramin, and inLatin islofepraminum.[3][4]
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^abcdLeonard BE (October 1987). "A comparison of the pharmacological properties of the novel tricyclic antidepressant lofepramine with its major metabolite, desipramine: a review".International Clinical Psychopharmacology.2 (4):281–297.doi:10.1097/00004850-198710000-00001.PMID2891742.
^abKerihuel JC, Dreyfus JF (1991). "Meta-analyses of the efficacy and tolerability of the tricyclic antidepressant lofepramine".The Journal of International Medical Research.19 (3). SAGE Publications:183–201.doi:10.1177/030006059101900304.PMID1834491.S2CID22873432.
^abcdefJoint Formulary Committee (2017).BNF 73 (British National Formulary) March 2017. London, UK: Pharmaceutical Press. pp. 354–355.ISBN978-0-85711-276-7.
^abcdeRoth 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. Retrieved7 May 2022.
^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. Retrieved7 May 2022.
^abcTatsumi M, Groshan K, Blakely RD, Richelson E (December 1997). "Pharmacological profile of antidepressants and related compounds at human monoamine transporters".European Journal of Pharmacology.340 (2–3):249–258.doi:10.1016/s0014-2999(97)01393-9.PMID9537821.
^abcdOwens MJ, Morgan WN, Plott SJ, Nemeroff CB (December 1997). "Neurotransmitter receptor and transporter binding profile of antidepressants and their metabolites".The Journal of Pharmacology and Experimental Therapeutics.283 (3):1305–1322.PMID9400006.
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^abToll L, Berzetei-Gurske IP, Polgar WE, Brandt SR, Adapa ID, Rodriguez L, et al. (March 1998). "Standard binding and functional assays related to medications development division testing for potential cocaine and opiate narcotic treatment medications".NIDA Research Monograph.178:440–466.PMID9686407.
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^Muth EA, Haskins JT, Moyer JA, Husbands GE, Nielsen ST, Sigg EB (December 1986). "Antidepressant biochemical profile of the novel bicyclic compound Wy-45,030, an ethyl cyclohexanol derivative".Biochemical Pharmacology.35 (24):4493–4497.doi:10.1016/0006-2952(86)90769-0.PMID3790168.
^abcdAppl H, Holzammer T, Dove S, Haen E, Strasser A, Seifert R (February 2012). "Interactions of recombinant human histamine H₁R, H₂R, H₃R, and H₄R receptors with 34 antidepressants and antipsychotics".Naunyn-Schmiedeberg's Archives of Pharmacology.385 (2):145–170.doi:10.1007/s00210-011-0704-0.PMID22033803.S2CID14274150.
^abcdeStanton T, Bolden-Watson C, Cusack B, Richelson E (June 1993). "Antagonism of the five cloned human muscarinic cholinergic receptors expressed in CHO-K1 cells by antidepressants and antihistaminics".Biochemical Pharmacology.45 (11):2352–2354.doi:10.1016/0006-2952(93)90211-e.PMID8100134.
^abcAndersen J, Kristensen AS, Bang-Andersen B, Strømgaard K (July 2009). "Recent advances in the understanding of the interaction of antidepressant drugs with serotonin and norepinephrine transporters".Chemical Communications (25):3677–3692.doi:10.1039/b903035m.PMID19557250.
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