Nefopam hydrochloride

Chemical properties

White to Off-White Solid

Originator

Ajan,Kettelhack Riker,W. Germany,1976

The Uses of Nefopam hydrochloride

Nefopam hydrochloride has been used as a standard for the quantitative determination of tramadol by gas chromatography–mass spectrometry (GC/MS).

The Uses of Nefopam hydrochloride

A cyclized analog of orphenadrine and diphenhydramine; representative of a new class of centrally acting skeletal muscle relaxants, the benzoxazocines. Analgesic; antidepressant.

Manufacturing Process

The starting material is prepared by reacting 2-benzoylbenzoic acid with thionyl chloride and then with 2-methylaminoethanol. 20.0 grams (0.07 mol) of N-(2-hydroxyethyl)-N-methyl-o-benzoylbenzamide is suspended in 100 ml tetrahydrofuran and then slowly added in small portions to a solution of 5.5 grams (0.14 mol) of lithium aluminum hydride in 150 ml tetrahydrofuran with cooling and stirring. The mixture is then refluxed for 18 hours, cooled and then to it is successively added 5.5 ml water, 5.5 ml of 3.75 N sodium hydroxide and 16 ml water. After removal of precipitated salts by filtration, the solution remaining is concentrated under reduced pressure and the residue dried to yield 19.5 grams of crude product. Yield after conversion to the hydrochloride salt and recrystallization is 17.0 grams (89%), MP 128° to 133°C.
5-methyl-1-phenyl-1,3,4,6-tetrahydro-5H-benz[f] -2,5-oxazocine is prepared as follows. 3.0 grams (0.011 mol) of 2-([N-(2-hydroxyethyl)-Nmethyl]amino)methylbenzhydrol, prepared as described above, 3.0 grams ptoluenesulfonic acid and 15 ml benzene are heated together with stirring until all the benzene is distilled off. The residual oil is heated to 105°C and held at this temperature for 1 hour, then cooled and dissolved in 30 ml water. This aqueous solution is then basified to pH 10.0 with 12 N sodium hydroxide, extracted with ether, and the extracts washed with water, dried over anhydrous sodium sulfate and the solvent removed under reduced pressure. The 2.26 grams (81%) oil remaining is converted to the hydrochloride salt, MP 238° to 242°C.

brand name

Acupan (3M Pharmaceuticals).

Therapeutic Function

Muscle relaxant, Antidepressant

Biochem/physiol Actions

Nefopam is a centrally-acting analgesic drug of the benzoxazocine chemical class. Nefopam is a non-opioid, but has a potentiating effect on morphine and other opioids. Its mechanism of action is not certain, but may involve its action as a dopamine/serotonin/norepinephrine reuptake inhibitor.

Clinical Use

Analgesic for moderate pain

Drug interactions

Potentially hazardous interactions with other drugs
Antidepressants: avoid MAOIs; tricyclics possibly increased risk of side effects.

Metabolism

Extensively metabolised in the liver to produce active metabolites. It is mainly excreted in the urine. About 8% of a dose is excreted via the faeces.