Propylhexedrine

Propylhexedrine

Systematic (IUPAC) name
(RS)-N,α-dimethyl-cyclohexylethylamine
Clinical data
AHFS/Drugs.com	monograph
Pregnancy cat.	C
Legal status	Unscheduled (US Federal) Schedule varies (US States) Schedule V (Canada Exempted from the application of the CDSA[1]
Routes	Medical: Intranasal (inhaler) and oral. Recreational: Oral and parenteral routes.
Pharmacokinetic data
Bioavailability	?
Metabolism	?
Half-life	?
Excretion	?
Identifiers
CAS number	3595-11-7 Y
ATC code	?? ?
PubChem	CID 7558
DrugBank	DB06714
ChemSpider	7277 Y
UNII	LQU92IU8LL Y
KEGG	D05637 Y
Synonyms	Hexahydrodesoxyephedrine; Hexahydromethamphetamine; Dimethylcyclohexaneethanamine
Chemical data
Formula	C10H21N
Mol. mass	155.29 g/mol
SMILES	eMolecules & PubChem
InChI InChI=1S/C10H21N/c1-9(11-2)8-10-6-4-3-5-7-10/h9-11H,3-8H2,1-2H3 Y Key:JCRIVQIOJSSCQD-UHFFFAOYSA-N Y
Y(what is this?)  (verify)

Propylhexedrine (Benzedrex, Obesin) is a stimulant drug related to methamphetamine. It is used mainly to provide temporary symptomatic relief of nasal congestion due to colds, allergies and allergic rhinitis. Being a vasoconstrictor used to decongest nasal mucosa, it is administered by inhalation.

Propylhexedrine is most commonly found in over-the-counter Benzedrex inhaler. 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 U.S. Schedule II status (second highest abuse potential with limited medicinal use). Propylhexedrine has also seen use in Europe as an appetite suppressant under the trade name Obesin^[2] 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.^[2] Levopropylhexedrine is also used as an anorectic under the brand name Eventin.

Chemistry

Freebase propylhexedrine is a volatile, oily liquid at room temperature. The slow vaporization of freebase propylhexedrine allows it to be administered via inhalation.^[3]

Propylhexedrine can be reacted with an acid like hydrochloric acid to form a salt form of propylhexedrine. Propylhexedrine hydrochloride has the appearance of a white powder or crystals.^[4]

Propylhexedrine is structurally similar to methamphetamine. The only difference in the two compounds is that an alicyclic cyclohexyl group is used in lieu of the aromatic phenyl group of methamphetamine. It is because of this that propylhexedrine is not an amphetamine, nor even a phenethylamine, but instead can be referred to as a cycloalkylamine.

Propylhexedrine, like amphetamine and methamphetamine, is a chiral compound (the α-carbon is chiral, like in its amphetamine cousins). The propylhexedrine contained in Benzedrex inhalers is racemic (RS)-propylhexedrine as the freebase. (S)-Propylhexedrine, also known as levopropylhexedrine, is believed to be the more biologically active isomer of the two.^[5] (S)-Propylhexedrine can be synthesized from dextro-methamphetamine.^[6]

Pharmacology

The pharmacology of propylhexedrine is not understood fully, but it appears to act as an agonist at alpha-adrenergic receptors and it appears to reverse the transporters for dopamine (DA), norepinephrine (NE), and serotonin (5-HT) leading to these monoamines to be released from the vesicles to the cytoplasm and then from the cytoplasm to the synapses. This results in a net increase in levels of these monoamines in the synapses which correlates with increased activity at these receptors. Additionally propylhexedrine appears to antagonize the VMAT2 transporter, leading to a further increase in the aforementioned monoamines. The actions of propylhexedrine in this regard are similar to amphetamine's mode of action.^[7]

Contraindications

Propylhexedrine should never 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 cardiac disease should not use propylhexedrine.^[8]

Additionally drugs such as stimulants and sympathomimetics should not be taken along with propylhexedrine as this can lead to potentially dangerous spikes in blood pressure and irregular heart rhythms.^[9]

Medical use

Propylhexedrine is used for nasal congestion. Historically, it has also been used for weight loss.

Recreational use

Propylhexedrine has been reported to be used recreationally, obtained as freebase from the cotton rods that Benzedrex inhalers contain.

Effects

Propylhexedrine has sympathomimetic, adrenergic, vasocontricive and psychostimulant effects when taken above the medical dosage, the effects produced tend to be of the amphetamine type. Effects include increased sweating, talkativeness, euphoria, pupil dilation, emotional lability, anorexia, tachycardia, palpitations, dry mouth, bruxism, anxiety, dysphoria, increased aggressiveness, paranoia, headache, dizziness, slurred or impaired speech, rarely convulsions, serious heart problems; psychosis can occur.^[10]

Withdrawal effects can occur and include fatigue, depression, suicidal tendencies, hunger and extreme desire for sleep.

Recreational use potential

Propylhexedrine has a lower potential for abuse than other stimulants. This is partially because methods of its use are limited, unlike more commonly abused amphetamine, methamphetamine and methylphenidate. Oral ingestion being the most practical method of consumption, the inactive ingredients in a Benzedrex inhaler (menthol and lavender oil) are also ingested - most users report the taste and smell to be very unpleasant, resulting in "menthol burps" (frequent belching releasing the smell of the two) that often cause the user discomfort and sometimes nausea. Many drug users find that propylhexedrine has a very heavy "comedown" compared to the "high" it causes. The abuse potential is considered to be low enough that neither the DEA nor the WHO consider it a drug of concern at the present, unlike ephedrine and its salts which are known to be used as precursor chemicals in illicit manufacture of methamphetamine (and occasionally amphetamine). That said, propylhexedrine is controlled in some jurisdictions.

Injection risks

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 injection is dangerous and could result in serious bodily harm or death. IV use of propylhexedrine is known to cause transient diplopia and brainstem dysfunction, and deaths have been recorded in the medical literature. Typically, recorded cases of IV use are prepared by forming propylhexedrine HCl in a solution with hydrochloric acid, the solution is then heated to evaporate and the resulting crystals are dissolved in water for injection.^[11][12][13]

Drug risks

As with similar drugs, using propylhexedrine to keep oneself awake for extended amounts of time can lead to a temporary state of sleep deprivation during which an individual may experience hallucinations including auditory, visual and tactile (e.g. bugs crawling on or under the skin), paranoia, irritability and impaired memory.

Propylhexedrine, being a vasocontrictor and a stimulant, may carry a further risk as blood pressure and heart rate are raised, sometimes severely. Hypertension experienced by users of propylhexedrine can be dangerous, especially in those who have pre-existing blood pressure problems. The increase in heart rate can lead to lower levels of oxygen, discomfort, panic and in severe cases heart attack or serious arrhythmias. Again, this risk is higher if the user has existing heart problems.

Using propylhexedrine by ingesting the cotton rod contained in the Benzedrex inhaler may be dangerous. It appears that the cotton typically goes completely through the gastrointestinal tract and is then excreted, but there is the possibility of it causing an intestinal obstruction which is a medical emergency and can lead to infection and death. Currently there is no report of obstruction that occurred due to ingesting the Benzedrex cotton rod.^{[citation needed]}

See also

• Amphetamine
• Benzedrine
• Cyclopentamine
• Cypenamine
• Methamphetamine
• Tranylcypromine

References

1. ^ "Controlled Drugs and Substances Act". http://laws.justice.gc.ca/en/showdoc/cs/C-38.8/sc:5/20090817/en#anchorsc:5. Retrieved 20 August 2009. 
2. ^ ^{a b} Wesson DR (June 1986). "Propylhexdrine". Drug and Alcohol Dependence 17 (2–3): 273–8. doi:10.1016/0376-8716(86)90013-X. PMID 2874970. http://linkinghub.elsevier.com/retrieve/pii/0376-8716(86)90013-X. 
3. ^ Nasal Inhaler, US 4095596 
4. ^ Mancusi-Ungaro, H. R. Jr. M.D.; Decker, W. J. Ph.D.; Forshan, V. R. D. O.; Blackwell, S. J. M.D.; Lewis, S. R. M.D. (1983). "Tissue Injuries Associated With Parenteral Propylhexedrine Abuse". Journal of Trauma-Injury Infection & Critical Care 23 (7): 650. doi:10.1097/00005373-198307000-00114. http://journals.lww.com/jtrauma/Citation/1983/07000/Tissue_Injuries_Associated_With_Parenteral.114.aspx. 
5. ^ A. M. Lands, V. L. Nash, H. R. Granger and B. L. Dertinger (1947). "The Pharmacologic Activity of N-Methyl-β-cyclohexylisopropylamine Hydrochloride". JPET 89 (3): 382–385. http://jpet.aspetjournals.org/content/89/3/382.short. 
6. ^ Textbook of organic medicinal and pharmaceutical chemistry, Charles Owens Wilson, Ole Gisvold, Robert F. Doerge, page 491
7. ^ http://www.drugbank.ca/drugs/DB06714 Propylhexedrine's DrugBank Entry
8. ^ http://reference.medscape.com/drug/benzedrex-propylhexedrine-343411#5 Propylhexedrine Contraindications - Medscape
9. ^ http://www.nida.nih.gov/researchreports/prescription/prescription4.html#Safe Safety of mixing stimulants with medications - NIDA
10. ^ Fornazzari, L; Carlen, PL; Kapur, BM (1986). "Intravenous abuse of propylhexedrine (Benzedrex) and the risk of brainstem dysfunction in young adults". The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques 13 (4): 337–9. PMID 2877725. 
11. ^ "Proposed Rules". Federal Register 50 (10): 2226–2227. 
12. ^ Prince v. Ascher, 90 P.3d 1020 (2004).
13. ^ Fornazzari L, Carlen PL, Kapur BM. "Intravenous abuse of propylhexedrine (Benzedrex) and the risk of brainstem dysfunction in young adults." Canadian Journal of Neurological Science. 1986 Nov;13(4):337-9. PMID 2877725