|Trade names||Benzedrex, Obesin, others|
|Other names||Hexahydro-desoxyephedrine; Hexahydro-methamphetamine; Hydromethamphetamine; Dimethylcyclo-hexaneethanamine; Cycohexyliso-propylmethylamine; Propylhexedrinum|
|Main uses||Stuffy nose|
|Side effects||Burning, nasal discharge|
|Medical: Intranasal, by mouth|
Recreational: By mouth, by injection
|Onset of action||Within 5 min|
|Duration of action||Up to 2 hrs|
|Elimination half-life||4 ± 1.5 hours|
|Chemical and physical data|
|Molar mass||155.285 g·mol−1|
|3D model (JSmol)|
Propylhexedrine, sold under the brand names Benzedrex among others, is a medication used for a stuffy nose. It is used in the nose. Benefits begin within 5 minutes and may last for up to 2 hours. Use is not recommended for more than three days.
Common side effects include burning and nasal discharge. Other concerns include headache, high blood pressure, and psychosis. Safety in pregnancy is unclear. It works similar to amphetamines by causing small arteries to constrict.
Propylhexedrine came into commercial use in 1949. It is available over the counter. In the United States a delivery device costs about 13 USD as of 2021. It is not a controlled substance in the United States. It has also been used for weight loss and misused by people trying to get high.
For nasal congestion, the dosage is listed as four inhalations (two inhalations per nostril) every two hours for adults and children 6–12 years of age. Each inhalation delivers 0.4 to 0.5 milligram (400 to 500 μg) in 800 millilitres of air.
Propylhexedrine should not be used if an MAOI has been used in the past 14 days, or is being currently used, as this can lead to a hypertensive crisis. People with cardiovascular disease should not use propylhexedrine.
Additionally, drugs such as stimulants and sympathomimetics should not be taken with propylhexedrine, as this can lead to potentially dangerous spikes in blood pressure and irregular heart rhythms.
There is one case of death where a combination of propylhexedrine, acetaminophen, morphine, promethazine, and kratom was detected. However the study indicates that propylhexedrine was most likely the principal cause of death.
Propylhexedrine is a TAAR1 agonist, like amphetamine.[failed verification] Consequently, it reverses the transporters for dopamine, norepinephrine, and serotonin, leading to a release of monoamines from presynaptic vesicles into the synaptic cleft. The increased level of monoamines within the synapse results in increased activity at their respective receptors. Additionally, propylhexedrine appears to inhibit VMAT2, leading to a further increase in the aforementioned monoamines. The pharmacological actions of propylhexedrine are similar to that of structurally similar stimulant phenethylamines, such as amphetamine.
Freebase propylhexedrine is a volatile, oily liquid at room temperature. The slow evaporation of freebase propylhexedrine allows it to be administered via inhalation. As an amine, it can easily be protonated to form various salts, such as propylhexedrine hydrochloride, propylhexedrine citrate, or propylhexedrine acetate, depending on the acid used. These salts are stable, clear to off-white crystalline substances that readily dissolve in water.
Propylhexedrine is structurally similar to phenylethylamines, with the only structural difference being the substitution of an alicyclic cyclohexyl group for the aromatic phenyl group of phenethylamine. Propylhexedrine is not an amphetamine, nor even a phenethylamine, but instead can be referred to as a cycloalkyl amine, or more specifically a cyclohexylethylamine being the N,a-dimethyl derivative of 2-cyclohexylethylamine.
Propylhexedrine is a chiral compound (the α-carbon is chiral), and the active ingredient contained in Benzedrex inhalers is racemic (RS)-propylhexedrine as the free base. (S)-Propylhexedrine, also known as levopropylhexedrine, is believed to be the more biologically active isomer of the two. (S)-Propylhexedrine can be synthesized from dextromethamphetamine.
Benzedrex was first manufactured by Smith, Kline and French after the Benzedrine inhaler, which contained racemic amphetamine, became unavailable following the placement of amphetamines on the US Schedule II status (highest abuse potential, yet with accepted medicinal uses). Benzedrex is currently manufactured by B.F. Ascher & Co. Inc. Pharmaceuticals.
Propylhexedrine has also been useed in Europe as an appetite suppressant under the trade name Obesin and in the anticonvulsant preparation barbexaclone its S-isomer (levopropylhexedrine or L-propylhexedrine) is bonded with phenobarbital for the purpose of offsetting the barbiturate-induced sedation. Levopropylhexedrine is also used as an anorectic under the brand name Eventin.
Society and culture
Propylhexedrine is used recreationally in a manner similar to amphetamine, methamphetamine, and dextroamphetamine. Users report a high similar to other amphetamines, but often much more euphoric. Compared to both amphetamine and methamphetamine, propylhexedrine has a much shorter duration of action (which is generally considered undesirable by recreational users). In addition, propylhexedrine products are manufactured using delivery devices (such as sub-recreational-dosage inhalers) that are difficult (or nearly impossible) to consume effectively (at recreational doses) via non-oral routes of administration, further limiting its ability to match or replace other amphetamine-related stimulants for recreational use. The negative physical side effects of propylhexedrine at recreational doses are often notably worse than non-IV methamphetamine, amphetamine, and other commonly abused stimulants, making it sub-optimal for long term recreational use.
Long-term health problems may develop from daily use. Compared to dextroamphetamine, it is a heavier strain on the cardiovascular system, and the risk of heart damage increases when used daily. Unlike amphetamine, propylhexedrine's serotonin-releasing properties have the potential to cause long term negative side effects similar to MDMA abuse, though the degree in which decreased serotonergic neurotransmission occurs as a result of recreational propylhexedrine usage is largely unclear in the relevant literature.
Propylhexedrine has sympathomimetic, adrenergic, vasoconstrictive and psychostimulant effects when taken above the medical dosage. Effects include increased sweating, talkativeness, mydriasis, emotional lability, anorexia, tachycardia, palpitations, dry mouth, bruxism, anxiety, euphoria or dysphoria, increased aggressiveness, paranoia, headache, dizziness, psychosis, slurred or impaired speech, rarely convulsions and serious heart problems. Propylhexedrine can also cause swelling, dryness and irritation of mucous membranes.
While propylhexedrine is limited in a number of administration routes, attempts to extract the drug from the nasal inhaler and then inject it have been reported. Recreational use by intravenous injection (IV) is dangerous and could result in serious bodily harm or death. IV use of propylhexedrine is known to cause mild side-effects such as transient diplopia as well as some serious (and potentially fatal) effects such as brainstem dysfunction, and deaths have been recorded in the medical literature. Typically, recorded cases of IV use are prepared by placing propylhexedrine freebase in a solution with hydrochloric acid to form propylhexedrine HCl, the solution is then heated to evaporate the solvent and the resulting crystals are dissolved in water for injection.
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