23047-25-8

Lofepramine is a first generation tricyclic antidepressant that is extensively metabolized to desipramine. It potently inhibits serotonin and norepinephrine transporters (K_ds = 70 and 5.4 nM, respectively) and less potently antagonizes serotonin, histamine, and muscarinic receptors.

Light Yellow Solid

Gamonil,E. Merck

Psychotropic drug related to imipramine. Antidepressant

ChEBI: Lofepramine is a dibenzoazepine, a member of monochlorobenzenes, a tertiary amino compound and an aromatic ketone. It has a role as an antidepressant.

9.8 parts of 10,11-dihydro-5H-dibenzo[b,f]azepine are dissolved in 10 parts of dry toluene and 3.1 parts of sodium amide are added and the mixture is refluxed and stirred for four hours. A solution of 13.5 parts of 1-(4- chlorophenyl)-2-[(3-chloropropyl)methylamino]ethanone in 20 parts of dry toluene is added dropwise and the mixture is stirred and refluxed for eight hours.
After cooling to room temperature water is carefully added to the reaction mixture and the toluene solution is extracted with water to which hydrochloric acid is added so that the aqueous phase obtains the pH-value of 5. The aqueous extract is discarded and the toluene phase is evaporated to dryness in vacuum. The residue is dissolved in 50 parts of methanol. Hydrogen gas is introduced to give the crystalline hydrochloride 1-(4-chlorophenyl)-2-((3- (10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)methylamino)ethanone; MP: 154°-156°C. The hydrochloride may be removed by adding an equivalent of any base (triethyl amine, sodium hydroxide and so on).

Antidepressant

Serotonin and noradrenalin re-uptake inhibitor (SNRI) that is metabolized to desipramine. Produces inhibition of liver tryptophan pyrollase activity in vitro and displays antidepressant properties in vivo .

Lofepramine differs from imipramine by the attachment of a p-chlorophenacyl moiety to the N-aminopropyl side chain. This change confers enhanced lipophilicity and the potential of more rapid distribution into the CNS with greater in vitro affinity and selectivity for NET. Its mechanism of antidepressant action is attributed to its rapid metabolism to the secondary amine metabolite, desipramine, which selectively inhibits the neuronal uptake of NE.