indication

Used in the management of exogenous obesity as a short-term adjunct (a few weeks) in a regimen of weight reduction based on caloric restriction.

pharmacology

Diethylpropion is a sympathomimetic stimulant drug marketed as an appetite suppressant. Chemically, it is the N,N-diethyl analog of cathinone. Its mechanism of action is similar to other appetite suppressants such as sibutramine, phentermine and dextroamphetamine.

mechanism of action

Diethylpropion is an amphetamine that stimulates neurons to release or maintain high levels of a particular group of neurotransmitters known as catecholamines; these include dopamine and norepinephrine. High levels of these catecholamines tend to suppress hunger signals and appetite. Diethylpropion (through catecholamine elevation) may also indirectly affect leptin levels in the brain. It is theorized that diethylpropion can raise levels of leptin which signal satiety. It is also theorized that increased levels of the catecholamines are partially responsible for halting another chemical messenger known as neuropeptide Y. This peptide initiates eating, decreases energy expenditure, and increases fat storage.

toxicity

The reported oral LD₅₀ for mice is 600 mg/kg, for rats is 250 mg/kg and for dogs is 225 mg/kg. Manifestation of acute overdosage include restlessness, tremor, hyperreflexia, rapid respiration, confusion, assaultiveness, hallucinations, and panic states.

biotransformation

Extensively metabolized through a complex pathway of biotransformation involving N-dealkylation and reduction. Many of these metabolites are biologically active and may participate in the therapeutic action of diethylpropion.

absorption

Diethylpropion is rapidly absorbed from the GI tract after oral administration.

half life

Using a phosphorescence assay that is specific for basic compounds containing benzoyl group, the plasma half-life of the aminoketone metabolites is estimated to be between 4 to 6 hours.

route of elimination

Diethylpropion is rapidly absorbed from the GI tract after oral administration and is extensively metabolized through a complex pathway of biotransformation involving N-dealkylation and reduction. Diethylpropion and/or its active metabolites are believed to cross the blood-brain barrier and the placenta. Diethylpropion and its metabolites are excreted mainly by the kidney.

drug interactions

Acetophenazine: Decreased anorexic effect, may increase psychotic symptoms

Chlorpromazine: Decreased anorexic effect, may increase psychotic symptoms

Ethopropazine: Decreased anorexic effect, may increase psychotic symptoms

Fluoxetine: Risk of serotoninergic syndrome

Fluphenazine: Decreased anorexic effect, may increase psychotic symptoms

Fluvoxamine: Risk of serotoninergic syndrome

Guanethidine: Diethylpropion may decrease the effect of guanethidine.

Isocarboxazid: Possible hypertensive crisis

Mesoridazine: Decreased anorexic effect, may increase psychotic symptoms

Methdilazine: Decreased anorexic effect, may increase psychotic symptoms

Methotrimeprazine: Decreased anorexic effect, may increase psychotic symptoms

Paroxetine: Risk of serotoninergic syndrome

Perphenazine: Decreased anorexic effect, may increase psychotic symptoms

Phenelzine: Possible hypertensive crisis

Prochlorperazine: Decreased anorexic effect, may increase psychotic symptoms.

Promazine: Decreased anorexic effect, may increase psychotic symptoms

Promethazine: Decreased anorexic effect, may increase psychotic symptoms.

Propericiazine: Decreased anorexic effect, may increase psychotic symptoms.

Propiomazine: Decreased anorexic effect, may increase psychotic symptoms

Rasagiline: Possible hypertensive crisis

Thiethylperazine: Decreased anorexic effect, may increase psychotic symptoms

Thioridazine: Decreased anorexic effect, may increase psychotic symptoms

Tranylcypromine: Possible hypertensive crisis

Trifluoperazine: Decreased anorexic effect, may increase psychotic symptoms

Triflupromazine: Decreased anorexic effect, may increase psychotic symptoms

Trimeprazine: Decreased anorexic effect, may increase psychotic symptoms

Venlafaxine: Risk of serotoninergic syndrome