Product Code Database
Lofepramine, sold under the brand names Gamanil, Lomont, and Tymelyt among others, is a tricyclic antidepressant (TCA) which is used to treat depression. 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 neurotransmitters norepinephrine and serotonin in the synapse, by inhibiting their reuptake. 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.
Lofepramine is not available in the United States, Canada, Australia or New Zealand, although it is available in Ireland, Japan, South Africa and the United Kingdom, among other countries.
Lofepramine is an efficacious antidepressant with about 64% patients responding to it.
And in those being treated with amiodarone or terfenadine.
Dropout incidence due to side effects is about 20%.
Side effects with unknown frequency include (but are not limited to):
| + Lofepramine (and metabolite) | ||||
| Values are Ki (nM). The smaller the value, the more strongly the drug binds to the site. | ||||
Lofepramine is a strong inhibitor of norepinephrine reuptake and a moderate inhibitor of serotonin reuptake. It is a weak-intermediate level antagonist of the muscarinic acetylcholine receptors.
Lofepramine has been said to be a prodrug of desipramine, although there is also evidence against this notion.
Pharmacokinetics
Lofepramine is extensively metabolized, via cleavage of the p-chlorophenacyl group, to the TCA, desipramine, in humans. However, it is unlikely this property plays a substantial role in its overall effects as lofepramine exhibits lower toxicity and anticholinergic relative to desipramine while retaining equivalent antidepressant efficacy. The p-chlorophenacyl group is metabolized to p-chlorobenzoic acid which is then conjugated with glycine and excreted in the urine. The desipramine metabolite is partly secreted in the faeces. Other routes of metabolism include hydroxylation, glucuronidation, N-dealkylation and N-oxidation.
Chemistry
Lofepramine is a tricyclic compound, specifically a dibenzazepine, and possesses three rings fused together with a side chain attached in its chemical structure. Other dibenzazepine TCAs include imipramine, desipramine, clomipramine, and trimipramine. Lofepramine is a tertiary amine TCA, with its side chain-demethylation metabolite desipramine being a secondary amine. Unlike other tertiary amine TCAs, lofepramine has a bulky 4-chlorobenzoylmethyl substituent on its amine instead of a methyl group. Although lofepramine is technically a tertiary amine, it acts in large part as a prodrug of desipramine, and is more similar to secondary amine TCAs in its effects. Other secondary amine TCAs besides desipramine include nortriptyline and protriptyline. The chemical name of lofepramine is N-(4-chlorobenzoylmethyl)-3-(10,11-dihydro-5 H-dibenzo b, fazepin-5-yl)-N-methylpropan-1-amine and its free base form has a chemical formula of C26H27ClN2O with a molecular weight of 418.958 g/mol. The drug is used commercially mostly as the hydrochloride salt; the free base form is not used. The CAS Registry Number of the free base is 23047-25-8 and of the hydrochloride is 26786-32-3.
History
Lofepramine was developed by Leo Läkemedel AB. It first appeared in the literature in 1969 and was patented in 1970. The drug was first introduced for the treatment of depression in either 1980 or 1983.
Society and culture
Generic names
Lofepramine is the generic term of the drug and its and , while lofepramine hydrochloride is its , , and . Its generic name in French language and its are lofépramine, in Spanish language and Italian language and its are lofepramina, in German language is lofepramin, and in Latin language is lofepraminum.
Brand names
Brand names of lofepramine include Amplit, Deftan, Deprimil, Emdalen, Gamanil, Gamonil, Lomont, Tymelet, and Tymelyt.
Availability
In the United Kingdom, lofepramine is marketed (as the hydrochloride salt) in the form of 70 mg tablets and 70 mg/5 mL oral suspension.
Research
Fatigue
A formulation containing lofepramine and the amino acid L-phenylalanine is under investigation as a treatment for fatigue as of 2015.
Categories: 4-chlorophenyl Compounds, Alpha-1 Blockers, Amines, Antihistamines, Dibenzazepines, Ketones, M1 Receptor Antagonists, M2 Receptor Antagonists, M3 Receptor Antagonists, M4 Receptor Antagonists, M5 Receptor Antagonists, Norepinephrine Reuptake Inhibitors, Prodrugs, Serotonin Receptor Antagonists, Tricyclic Antidepressants
|
|
