Propylhexedrine is used to treat acute nasal congestion related to common cold, allergies and hay fever. For nasal congestion, the dosage is listed as four inhalations every two hours for adults and children 6–12 years of age. Each inhalation delivers 0.4 to 0.5 milligram in 800 millilitres of air. Historically, it has also been used for weight loss, typically at doses from 5 to 30 milligrams.
Contraindications
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.
Pharmacology
Propylhexedrine is a TAAR1 agonist, like amphetamine. 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.
Metabolism
Propylhexedrine undergoes metabolism to form various metabolites including norpropylhexedrine, cyclohexylacetoxime, cis- and trans-4-hydroxypropylhexedrine.
Chemistry
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 alicycliccyclohexyl 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 cycloalkylamine. Propylhexedrine is a chiral compound, and the active ingredient contained in Benzedrex inhalers is racemic -propylhexedrine as the free base. -Propylhexedrine, also known as levopropylhexedrine, is believed to be the more biologically active isomer of the two. -Propylhexedrine can be synthesized from dextromethamphetamine.
Synthesis
Propylhexedrine can be synthesized starting with cyclohexylacetone in a similar fashion to the phenylacetone synthesis of methamphetamine. However, more commonly propylhexedrine is prepared by reacting methamphetamine with Adams' catalyst, reducing methamphetamine's aromatic ring to a cyclohexyl moiety.
Propylhexedrine is used recreationally in a manner similar to amphetamine, methamphetamine, and dextroamphetamine. Users report a high that is often comparable to clandestine racemic amphetamine, noticeably inferior to dextroamphetamine-majority amphetamine products, and significantly inferior to dextroamphetamine or methamphetamine. Compared to both amphetamine and methamphetamine, propylhexedrine has a much shorter duration of action. In addition, propylhexedrine products are manufactured using delivery devices that are difficult to consume effectively 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.
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 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 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.
