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Propylhexedrine
Left: (S)-Propylhexedrine
Right: (R)-Propylhexedrine
Clinical data
Trade namesBenzedrex, Obesin, Dristan Inhaler, and others
Other names
  • Hexahydrodesoxyephedrine
  • Cyclohexylisopropylmethylamine
  • 1-cyclohexyl-2-methylaminopropane
AHFS/Drugs.comMonograph
Pregnancy
category
  • C
Routes of
administration		Medical: Intranasal (inhaler)
Recreational: Oral and parenteral routes
ATC code
Legal status
Legal status
Pharmacokinetic data
Elimination half-life4 ± 1.5 hours
Identifiers
  • (±)-1-cyclohexyl-N-methylpropan-2-amine
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
CompTox Dashboard (EPA)
ECHA InfoCard100.002.673 Edit this at Wikidata
Chemical and physical data
FormulaC10H21N
Molar mass155.285 g·mol−1
3D model (JSmol)
ChiralityRacemic mixture
  • N(C(CC1CCCCC1)C)C
  • InChI=1S/C10H21N/c1-9(11-2)8-10-6-4-3-5-7-10/h9-11H,3-8H2,1-2H3 checkY
  • Key:JCRIVQIOJSSCQD-UHFFFAOYSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Propylhexedrine, commonly sold under the brand name Benzedrex, is an alkylamine primarily utilized as a topical nasal decongestant.[1] Its main indications are relief of congestion due to colds, allergies, and allergic rhinitis.[2] Propylhexedrine was first used medically in 1949, with the release of Benzedrex by Smith, Kline & French, and it has been used, mainly within the United States, since then.[3]

Medical use

[edit]

Propylhexedrine is used to treat acute nasal congestion related to the common cold, allergies and hay fever. 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 milligrams (400 to 500 μg) in 800 millilitres of air.[4][2][5] Use is not to exceed three days.[2]

Historically, it has also been used for weight loss in oral tablet preparations at a dose of 25 milligrams.[6][7] No medications containing propylhexedrine are currently approved for weight loss in any country since roughly 1976.[8]

Contraindications

[edit]

Propylhexedrine should not be used if a MAOI has been used in the past 14 days or is currently in use by a person.[2]

Unlike other topical decongestants, propylhexedrine is not required to carry a warning against use in individuals with hypertension.[9]

Propylhexedrine is not recommended in individuals younger than six years of age.[10] There is at least one case of reported accidental poisoning resulting from child access to a propylhexedrine product.[11]

Adverse effects

[edit]

When used as an inhaler, the most common adverse effects warned about for propylhexedrine are temporary discomfort (e.g., stinging or burning sensations) or rebound congestion.[2] The sharing of propylhexedrine inhalers may spread infection.[2] The occurrence of these adverse effects is uncommon as propylhexedrine is generally recognized as safe and effective.[12] However, the use of propylhexedrine products in manners not intended by their labeling can result in severe adverse effects not typically encountered in therapeutic settings.[13][14][15] The outcomes of improperly using propylhexedrine products can include hospitalization, disability, or even death.[12] Public health agencies such as the FDA have advised propylhexedrine products only be used in the manners directed on their label.[12]

Overdose

[edit]

Reports of overdoses from propylhexedrine have been documented, but they are uncommon.[16] Most instances of overdoses attributed to propylhexedrine have been the result of improper use of a propylhexedrine product in a manner not intended by its labeling for (non-medical) recreational purposes.[13] As noted by the FDA, the most common symptoms of propylhexedrine overdose are the following: "...[R]apid heart rate, agitation, high blood pressure, chest pain, tremor, hallucinations, delusions, confusion, nausea, and vomiting."[13] The use of propylhexedrine products in manners inconsistent with their labeling has proven fatal in some cases.[17][18] Propylhexedrine products are considered to be safe and effective if used as intended.[13] Regardless, medical attention should be sought in the case of suspected overdose.[19]

Interactions

[edit]

Most of propylhexedrine's interactions with other medications have to do with its ability to constrict blood vessels. Propylhexedrine’s most serious interaction is with monoamine oxidase inhibitors, which are contraindicated.[2] Monoamine oxidase inhibitors are used, albeit uncommonly, as an antidepressant.[20] Nonetheless, caution should be exercised when administering propylhexedrine concurrently with other medicines.

Pharmacology

[edit]

Mechanism of action

[edit]

Propylhexedrine works mainly as an adrenergic agonist, when used at therapeutic doses in an inhaler dosage form.[21] This restricts the blood vessels in the nose and reduces swelling; thereby, it relieves nasal congestion.[22] At higher doses, propylhexedrine affects the central nervous system as a norepinephrine–dopamine releasing agent.[23] Propylhexedrine likely exerts such effects in a manner similar to related alkylamines such as cyclopentamine, methylhexanamine, and tuaminoheptane.[24][25][26] In addition, propylhexedrine further releases monoamines through TAAR1 agonism and VMAT2 inhibition.[21] Propylhexedrine also exhibits antihypotensive effects.[27]

Pharmacokinetics

[edit]
Metabolism of propylhexedrine[28]

Propylhexedrine undergoes metabolism via N-demethylation, C-oxidation, N-oxidation, dehydrogenation, and hydrolysis to form various metabolites such as norpropylhexedrine, cyclohexylacetoxime, cyclohexylacetone, and 4-hydroxypropylhexedrine.[28]

Chemistry

[edit]
Hydrochloride salt of propylhexedrine. The off-brown color gives rise to the slang term for this salt: "peanut butter".[29]

Freebase propylhexedrine is a volatile, oily liquid at room temperature. The slow evaporation of freebase propylhexedrine allows it to be administered via inhalation.[30] The evaporation of the freebase also accounts for the limited shelf-life of propylhexedrine inhalers. Many of the salts of propylhexedrine are stable, clear to off-white crystalline substances that readily dissolve in water.[31]

Propylhexedrine is similar in chemical structure to phenylethylamines. Phenylethylamines and substituted phenethylamines are found in the core of many trace amines and sympathomimetic drugs. The main difference is the presence of an alicyclic cyclohexyl group instead of the aromatic phenyl group of a phenethylamine.

Propylhexedrine is a chiral compound. The active ingredient contained in Benzedrex inhalers is racemic (RS)-propylhexedrine as the free base.[4] (S)-Propylhexedrine, also known as levopropylhexedrine, is believed to be the more biologically active isomer of the two.[27] The dextrorotatory counterpart, which is mainly unused, is dextropropylhexedrine.

Synthesis

[edit]

Propylhexedrine can be synthesized from cyclohexylacetone through the reductive amination of an intermediary imine over an aluminum-mercury amalgam in the presence of a hydrogen source.[32]

However, propylhexedrine is more commonly prepared by the catalytic hydrogenation of methamphetamine over Adams' catalyst. This transforms methamphetamine's phenyl ring to a cyclohexyl moiety.[33]

Detection in bodily fluids

[edit]

Due to its structure, administration of propylhexedrine can lead to false positives for phenethylamine derivatives on urinalysis panels.[34] Propylhexedrine can be differentiated upon further analysis.[35]

History

[edit]

Propylhexedrine's medical use as a decongestant evolved from desires to find safer alternatives to previous agents.[3] After searching for such an agent, Dr. Glenn E. Ullyot patented propylhexedrine as a decongestant in 1948. This patent was issued for benefit of Smith, Kline & French.[36] Before it was sold nationally in the United States, propylhexedrine underwent market trials in California. These market trials began on July 15, 1949.[37] Propylhexedrine (under the brand name Benzedrex) was first introduced into interstate commerce on August 4, 1949.[38]

An early Benzedrex inhaler, c. 1950s manufactured by Smith, Kline & French that includes the synonym "1-cyclohexyl-2-methylaminopropane"

Approval for use in the United Kingdom soon followed in 1956.[16] Later, approval for use in Canada was granted in 1998.[39] In 2023, B. F. Ascher & Co. decreased the amount of propylhexedrine in the Benzedrex inhaler from its historic 250 milligrams down to 175 milligrams.[40]

Barbexaclone, an anticonvulsant containing propylhexedrine, was used in Turkey until its withdrawal from the market in 2009. Barbexaclone's former niche in Turkish medicine is now largely occupied by levetiracetam.[41]

Manufacturing

[edit]

The manufacture of propylhexedrine products for therapeutic use is typically performed based on guidelines established in government regulations and pharmacopeia monographs.[42][5]

The illicit manufacture or diversion of propylhexedrine by clandestine chemists for use as a recreational drug has been documented in academic literature.[35] Similar to when opioids are manufactured clandestinely for recreational use, it is unlikely that propylhexedrine produced by clandestine chemists adheres to the standards for purity, identity, and strength required of therapeutic products.[43]

Society and culture

[edit]
[edit]

International control

[edit]

Propylhexedrine was placed under international control by the Convention on Psychotropic Substances in 1985. This action was reversed in 1991.[44]

Australia

[edit]

Propylhexedrine is an S4 substance in Australia.[45]

Brazil

[edit]

Propylhexedrine is a Class B1 substance in Brazil.[46]

Canada

[edit]

Propylhexedrine was long reported to be a Schedule V substance in Canada.[47] In 2022, this status changed and propylhexedrine has since been removed from control under the Controlled Drugs and Substances Act.[48]

Germany

[edit]

Propylhexedrine is regulated as a prescription medicine in Germany.[49] Initially, propylhexedrine products (namely Obesin) were available over-the-counter. However, this changed in the 1970s and propylhexedrine is now regulated as a prescription product in Germany.[8]

United Kingdom

[edit]

It was formerly a Class C substance in the United Kingdom, but was deregulated in 1995.[50] Propylhexedrine was used recreationally during a brief period in the 1970s after increased government regulation on earlier decongestants due to misuse.[51]

United States

[edit]

On the 4th of April 1988, propylhexedrine was designated a controlled substance (Schedule V) in the United States.[52] This was done to satisfy U.S. compliance with an international treaty. However, in 1991, this action was reversed and propylhexedrine was removed from control under the Controlled Substances Act. This was based on the opinion of the Drug Enforcement Administration that propylhexedrine did not warrant control.[53] The substance has remained unregulated under the Controlled Substances Act in the United States ever since. Furthermore, pursuant to DEA regulations, certain Benzedrex inhalers are specifically exempt from the Controlled Substances Act.[54][55] Propylhexedrine remains regulated under the laws of several U.S. states. These states include the states of Alaska,[56] Arizona,[57] Florida,[58] Georgia,[59] Idaho,[60] Kansas,[61] and Rhode Island.[62]

Recreational use

[edit]

Multiple public health agencies (most notably within the United States) have warned against the recreational use of propylhexedrine and advised for its use only as directed by a product's labeling; nonetheless it has been reported, through the literature as early as 1959, that propylhexedrine products have been used for recreational purposes.[6] Recreational use is potentially fatal, its risks are magnified when administering the substance through injection means, and the adverse effects of recreational propylhexedrine are more severe when compared to related substances.[63][64] The undesirable side effects of propylhexedrine at recreational doses are less tolerable compared to other substances that produce similar effects; consequently, propylhexedrine is less desirable for recreational use.[19][65][17] The fact that propylhexedrine is less potent than comparable substances has also limited recreational use.[66][67] Even in areas with prevalent substance use, the use of propylhexedrine was reported as non-significant.[16] The recreational use of nasal decongestant,[65][68] anorectic,[6] and anticonvulsant preparations[69] have all been reported. The recreational use of propylhexedrine products has been on the rise since the early 2000s.[23]

In 2021, the United States Food & Drug Administration issued the following warning[13] in regard to recreational use of propylhexedrine products in manners inconsistent with their labeling:

"...[T]he abuse and misuse of the over-the-counter (OTC) nasal decongestant propylhexedrine can lead to serious harm such as heart and mental health problems. Some of these complications, which include fast or abnormal heart rhythm, high blood pressure, and paranoia, can lead to hospitalization, disability, or death....Propylhexedrine is safe and effective when used as directed."

That same year, the Indian Health Service issued the following statement[14] in reference to the recreational use of propylhexedrine products:

"Only use propylhexedrine according to the instructions on the package label. Do not use it in ways other than inhalation. Seek medical attention immediately for by calling [emergency services] or Poison Control...for anyone using propylhexedrine who experiences [the following.] [These following reactions are] [s]evere anxiety or agitation, confusion, hallucinations, or paranoia[,] [r]apid heartbeat or abnormal heart rhythm[,] [or] [c]hest pain or tightness[.]"

A year later, in 2022, the U.S. Army published the following guidance[15] on propylhexedrine. The guidance states that recreational use of propylhexedrine is not permissible by service-members, can open its participants up to disciplinary action, and carries potentially fatal risks:

"When disciplining a member for suspected use of any drug, it is important to consult [legal counsel] on how to proceed, [according to the Office of Drug Demand Reduction]...This is especially important when the evidence supporting discipline consists of scientific reports and data that may require special assistance in their interpretation. In cases involving [propylhexedrine], legal consultation is highly recommended."

Put briefly, the Food & Drug Administration, Indian Health Service, and U.S. Army all advise individuals not to use propylhexedrine products for recreational purposes.

Economics

[edit]

Propylhexedrine, under the brand name Benzedrex, is sold online by retailers such as Amazon, eBay, and Walmart.[4] Propylhexedrine has been sold in some countries as an anorectic or as part of an anticonvulsant preparation; however, such products are not sold freely to consumers and require a physician's prescription.

Brand names

[edit]

Benzedrex inhaler

[edit]
Benzedrex inhaler, c. 2023, manufactured by B. F. Ascher & Co.

Propylhexedrine, as a nasal decongestant, is currently marketed under the trade name Benzedrex. The name Benzedrex was initially trademarked by Smith, Kline & French in 1944.[70] The brand was passed onto Menley James Laboratories (through a subsidiary, NuMark Laboratories) in 1990, and was finally acquired by B. F. Ascher & Co. in 1998.[71][72]

Dristan inhaler

[edit]
Dristan-brand inhaler, c. 1966 manufactured by Whitehall Laboratories

Propylhexedrine was also sold in inhaler form by Whitehall Laboratories (Wyeth) under the Dristan brand name as an inhaler.[73] In January 1966, propylhexedrine replaced mephentermine as the active ingredient in the product.[74] The Dristan inhaler has since been discontinued. Furthermore, Wyeth was acquired by Pfizer in 2009. All products currently sold under the Dristan brand are manufactured by Foundation Consumer Brands; Foundation Consumer Brands acquired the Dristan brand in 2020.[75] Foundation Consumer Brands is itself owned by Kelso & Company.

Obesin

[edit]
Obesin pill-case, c. 1974 manufactured by Fahlberg-List

Propylhexedrine has also seen use in Europe as an appetite suppressant, under the trade name Obesin.[37] Obesin has been referenced in literature dating back to the 1950s.[11][6] Obesin was manufactured by Fahlberg-List in East Germany from 1958 to around 1976. The discontinuation of Obesin was the result of increased regulatory restrictions on over-the-counter anorectics. These restrictions began to be imposed in 1974.[8] Fahlberg-List itself dissolved in 1995.

Maliasin

[edit]
Maliasin (Barbexaclone) carton, c. 2002 manufactured by Knoll Pharmaceuticals

Propylhexedrine is a component 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.[37] Barbexaclone has been known under the brand name of Maliasin, manufactured by Abbott Laboratories, as early as 1965.[76][77] Maliasin has also been manufactured by Knoll Pharmaceuticals; Knoll is a company acquired by Abbott Laboratories. In 2010, Abbott discontinued sale of its barbexaclone preparation in many countries.[78]

Eventin

[edit]

Levopropylhexedrine (the more active optical isomer of propylhexedrine) has been used as an appetite suppressant under the brand name Eventin. Eventin's use has been documented as early as 1958.[79]

References

[edit]
  1. ^ "Cold, Cough, Allergy, Bronchodilator, and Antiasthmatic Drug Products for Over-the-Counter Human Use". FDA. 7 June 2023. Archived from the original on 6 July 2023. Retrieved 5 July 2023.
  2. ^ a b c d e f g "BENZEDREX 09-19-2014- propylhexedrine inhalant". Daily Med. U.S. National Library of Medicine. Archived from the original on 16 July 2023. Retrieved 15 July 2023.
  3. ^ a b Schwarez J. "Sniffing Benzedrine Inhalers". Office for Science and Society. McGill University. Archived from the original on 16 July 2023. Retrieved 15 July 2023.
  4. ^ a b c "Benzedrex Inhaler". B. F. Ascher and Company. Archived from the original on 8 July 2023. Retrieved 8 July 2023.
  5. ^ a b "USP Monographs: Propylhexedrine Inhalant". United States Pharmacopeia. Archived from the original on 27 December 2023. Retrieved 27 December 2023.
  6. ^ a b c d Rose W (September 1959). "Arzneimittelsucht durch Mißbrauch von sogenannten Appetitzüglern (Obesin)". Archiv für Toxikologie (in German). 17 (5): 331–335. Bibcode:1959ArTox..17..331R. doi:10.1007/BF00577633. ISSN 1432-0738. S2CID 31539217.
  7. ^ Docherty JR (June 2008). "Pharmacology of stimulants prohibited by the World Anti-Doping Agency (WADA)". British Journal of Pharmacology. 154 (3): 606–622. doi:10.1038/bjp.2008.124. PMC 2439527. PMID 18500382.
  8. ^ a b c Winter E (1976). "Bemerkungen zu Drogenmißbrauch und -abhängigkeit vom Amphetamin- Typ unter besonderer Berücksichtigung des Amphetaminils (Aponeuron (R) )" [Comments on amphetamine-type drug abuse and dependence with special reference to amphetaminil (Aponeuron)]. Psychiatrie, Neurologie und medizinische Psychologie (in German). 28 (9): 513–525. ISSN 0033-2739. JSTOR 45253962.
  9. ^ Terrie YC (20 December 2017). "Decongestants and Hypertension: Making Wise Choices When Selecting OTC Medications". Pharmacy Times. December 2017 Heart Health. 83. Archived from the original on 30 January 2023. Retrieved 13 November 2023.
  10. ^ "Propylhexedrine". www.mskcc.org. Memorial Sloan Kettering Cancer Center. Archived from the original on 9 August 2023. Retrieved 16 July 2023.
  11. ^ a b Polster H (February 1965). "Über eine Vergiftung mit dem Appetitzügler Propylhexedrin "Obesin", bei einem 3 Ährigen Kinde" [About poisoning with the appetite suppressant propylhexedrine "Obesin" in a 3-year-old child]. Archiv für Toxikologie (in German). 20 (5): 271–273. doi:10.1007/BF00577551. PMID 14272412. S2CID 19812917.
  12. ^ a b c "Benzedrex (propylhexedrine): Drug Safety Communication". FDA. 25 March 2021. Archived from the original on 7 August 2023. Retrieved 16 July 2023.
  13. ^ a b c d e Center for Drug Evaluation and Research (15 April 2021). "FDA warns that abuse and misuse of the nasal decongestant propylhexedrine causes serious harm". FDA. U.S. Food and Drug Administration. Archived from the original on 23 February 2023. Retrieved 8 July 2023.
  14. ^ a b "Abuse and Misuse of Propylhexedrine Nasal Decongestant Causes Serious Harm". National Pharmacy & Therapeutics Committee. Indian Health Service. 2021. Archived from the original on 28 May 2023. Retrieved 3 November 2023.
  15. ^ a b Parrish A (26 October 2022). "FDA issues drug misuse guidance". United States Army. Archived from the original on 30 November 2022. Retrieved 13 November 2023.
  16. ^ a b c Smith DE, Wesson DR, Sees KL, Morgan JP (1 October 1988). "An epidemiological and clinical analysis of propylhexedrine abuse in the United States". Journal of Psychoactive Drugs. 20 (4): 441–442. doi:10.1080/02791072.1988.10472514. PMID 2907528.
  17. ^ a b Sturner WQ, Spruill FG, Garriott JC (July 1974). "Two propylhexedrine-associated fatalities: Benzedrine revisited". Journal of Forensic Sciences. 19 (3): 572–574. doi:10.1520/JFS10213J. PMID 4137337.
  18. ^ "Rise In Nasal Inhaler Abuse Worries Officials". The New York Times. 22 September 1985. p. 34. ISSN 0362-4331. Archived from the original on 30 August 2023. Retrieved 30 August 2023.
  19. ^ a b "Propylhexedrine (Benzedrex)". National Capital Poison Control. Archived from the original on 16 July 2023. Retrieved 16 July 2023.
  20. ^ "Monoamine oxidase inhibitors". Mayo Clinic. Retrieved 15 May 2024.
  21. ^ a b "Propylhexedrine". DrugBank. Archived from the original on 15 March 2012. Retrieved 8 July 2023.
  22. ^ "Decongestants". National Health Service. 18 October 2017. Archived from the original on 9 August 2023. Retrieved 9 August 2023.
  23. ^ a b Teja N, Dodge CP, Stanciu CN (October 2020). "Abuse, Toxicology and the Resurgence of Propylhexedrine: A Case Report and Review of Literature". Cureus. 12 (10): e10868. doi:10.7759/cureus.10868. PMC 7652022. PMID 33178521.
  24. ^ Small C, Cheng MH, Belay SS, Bulloch SL, Zimmerman B, Sorkin A, et al. (August 2023). "The Alkylamine Stimulant 1,3-Dimethylamylamine Exhibits Substrate-Like Regulation of Dopamine Transporter Function and Localization". The Journal of Pharmacology and Experimental Therapeutics. 386 (2): 266–273. doi:10.1124/jpet.122.001573. PMC 10353075. PMID 37348963.
  25. ^ Schmidt JL, Fleming WW (July 1964). "A Nonsympathomimetic Effect of Cyclopentamine and Beta-Mercaptoethylamine in the Rabbit Ileum". The Journal of Pharmacology and Experimental Therapeutics. 145: 83–86. PMID 14209515.
  26. ^ Delicado EG, Fideu MD, Miras-Portugal MT, Pourrias B, Aunis D (August 1990). "Effect of tuamine, heptaminol and two analogues on uptake and release of catecholamines in cultured chromaffin cells". Biochemical Pharmacology. 40 (4): 821–825. doi:10.1016/0006-2952(90)90322-c. PMID 2386550.
  27. ^ a b Lands AM, Nash VL (April 1947). "The pharmacologic activity of N-methyl-beta-cyclohexyl-isopropylamine hydrochloride". The Journal of Pharmacology and Experimental Therapeutics. 89 (4): 382–385. PMID 20295519.
  28. ^ a b Midha KK, Beckett AH, Saunders A (October 1974). "Identification of the major metabolites of propylhexedrine in vivo (in man) and in vitro (in guinea pig and rabbit)". Xenobiotica; the Fate of Foreign Compounds in Biological Systems. 4 (10): 627–635. doi:10.1080/00498257409169765. PMID 4428789.
  29. ^ Schaiberger PH, Kennedy TC, Miller FC, Gal J, Petty TL (August 1993). "Pulmonary hypertension associated with long-term inhalation of "crank" methamphetamine". Chest. 104 (2): 614–616. doi:10.1378/chest.104.2.614. PMID 8101799.
  30. ^ US granted 4095596, Grayson M, "Nasal Inhaler", issued 20 June 1978, assigned to Smithkline Corp. 
  31. ^ Mancusi-Ungaro HR, Decker WJ, Forshan VR, Blackwell SJ, Lewis SR (1983). "Tissue injuries associated with parenteral propylhexedrine abuse". Journal of Toxicology. Clinical Toxicology. 21 (3): 359–372. doi:10.1097/00005373-198307000-00114. PMID 6144800.
  32. ^ Lednicer D, Mitscher LA (1977). Organic Chemistry of Drug Synthesis. Vol. 1. New York, NY: Wiley. p. 37. ISBN 978-0-471-52141-9.
  33. ^ Zenitz BL, Macks EB, Moore ML (May 1947). "Preparation of some primary and secondary beta-cyclohexylalkylamines". Journal of the American Chemical Society. 69 (5): 1117–1121. doi:10.1021/ja01197a039. PMID 20240502.
  34. ^ Thurman EM, Pedersen MJ, Stout RL, Martin T (1992). "Distinguishing sympathomimetic amines from amphetamine and methamphetamine in urine by gas chromatography/mass spectrometry". Journal of Analytical Toxicology. 16 (1): 19–27. doi:10.1093/jat/16.1.19. PMID 1640694.
  35. ^ a b Johnson P, Briner RC (October 1992). "A Clandestine Laboratory Extracting Propylhexedrine from Benzedrex Inhalers". Journal of the Clandestine Laboratory Investigating Chemists Association. 2 (4): 25–28. Archived from the original on 9 August 2023.
  36. ^ US 2454746A, Ullyot GE, "Cyclohexylalkylamines", issued 1948-11-23, assigned to Smith Kline and French Laboratories Ltd. 
  37. ^ a b c Wesson DR (June 1986). "Propylhexdrine". Drug and Alcohol Dependence. 17 (2–3): 273–278. doi:10.1016/0376-8716(86)90013-X. PMID 2874970.
  38. ^ Grant G (4 August 1949). "Extension of remarks by representative Grant on H.R. 2969 - Bezedrine Inhalers" (PDF). Govinfo.gov. Volume 95 Issue 15. Government Publishing Office. p. A5052. Archived (PDF) from the original on 29 October 2023. Retrieved 29 October 2023 – via the Congressional Record.
  39. ^ "Propylhexedrine - NAPRA". (Canadian) National Association of Pharmacy Regulatory Authorities. Archived from the original on 15 July 2023. Retrieved 15 July 2023.
  40. ^ "BENZEDREX- propylhexedrine inhalant (06/23/2023)". Daily Med. U.S. National Library of Medicine. Archived from the original on 30 October 2023. Retrieved 30 October 2023.
  41. ^ Bolukbasi F, Delil S, Bulus E, Senturk A, Yeni N, Karaagac N (September 2013). "End of the barbexaclone era: an experience of treatment withdrawal". Epileptic Disorders. 15 (3): 311–313. doi:10.1684/epd.2013.0605. PMID 23981808. S2CID 39112148.
  42. ^ "Federal Register Vol. 41, No. 176" (PDF). Government Publishing Office. 9 September 1976. p. 38402. Archived from the original (PDF) on 16 July 2023.
  43. ^ Collier R (September 2013). "Street versions of opioids more potent and dangerous". CMAJ. 185 (12): 1027. doi:10.1503/cmaj.109-4535. PMC 3761004. PMID 23836854.
  44. ^ "Expert Committee on Drug Dependence's Twenty-Seventh Report" (PDF). World Health Organization. Expert Committee on Drug Dependence. 28 September 1990. Archived (PDF) from the original on 10 August 2023. Retrieved 3 July 2023.
  45. ^ "Therapeutic Goods (Poisons Standard—June 2024)". Australian Government. Archived from the original on 13 August 2024. Retrieved 13 August 2024.
  46. ^ Anvisa (31 March 2023). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 4 April 2023). Archived from the original on 3 August 2023. Retrieved 16 August 2023.
  47. ^ "Erowid Propylhexedrine (Benzedrex) Vault : Law". Erowid. Archived from the original on 16 July 2023. Retrieved 15 July 2023.
  48. ^ Government of Canada PW (31 August 2022). "Canada Gazette, Part 2, Volume 156, Number 18: Order Amending Schedule V to the Controlled Drugs and Substances Act (Novel Fentanyl Precursors)". Canada Gazette. Archived from the original on 31 March 2024. Retrieved 31 March 2024.
  49. ^ "Anlage 1 AMVV - Einzelnorm". Bundestag. Archived from the original on 30 November 2015. Retrieved 16 July 2023.
  50. ^ "The Misuse of Drugs Act 1971 (Modification) Order 1995". Office of Public Sector Information. Archived from the original on 7 August 2023. Retrieved 15 June 2009.
  51. ^ Wilson A (23 March 2016). "The blanket drugs ban is necessary, but won't solve the bigger problem – as I know from personal experience". The Conversation. Archived from the original on 30 April 2024. Retrieved 19 November 2023.
  52. ^ Lawn J (4 April 1988). "Schedules of Controlled Substances: Placement of Propylhexedrine and Pyrovalerone into Schedule V" (PDF). Isomer Design. Drug Enforcement Administration. Archived (PDF) from the original on 28 December 2022. Retrieved 9 July 2022.
  53. ^ Bonner R (3 December 1991). "Schedules of Controlled Substances: Removal of Propylhexedrine From Control" (PDF). Isomer Design. Drug Enforcement Administration. Archived (PDF) from the original on 28 December 2022. Retrieved 9 July 2022.
  54. ^ "Sec. 1308.22 Excluded substances". Code of Federal Regulations. Drug Enforcement Administration. Archived from the original on 31 May 2023. Retrieved 30 May 2023.
  55. ^ Haislip G (11 January 1989). "Excluded Non-narcotic Over-the-counter Substances" (PDF). Federal Register. Drug Enforcement Administration. Archived from the original (PDF) on 27 June 2023. Retrieved 26 June 2023.
  56. ^ "2014 Alaska Statutes :: Title 11 - Criminal Law :: Chapter 11.71 - Controlled Substances :: Article 02 - Standards and Schedules :: Sec. 11.71.180 Schedule VA". Justia Law. Archived from the original on 22 December 2023. Retrieved 22 December 2023.
  57. ^ "2005 Arizona Revised Statutes - :: Revised Statutes §13-3401 Definitions". Justia Law. Archived from the original on 22 December 2023. Retrieved 22 December 2023.
  58. ^ "2011 Florida Statutes :: TITLE XLVI — CRIMES :: Chapter 893 — Drug Abuse Prevention and Control :: 893.03 — Standards and schedules". Justia Law. Archived from the original on 22 December 2023. Retrieved 22 December 2023.
  59. ^ "2022 Georgia Code :: Title 16 - Crimes and Offenses :: Chapter 13 - Controlled Substances :: Article 2 - Regulation of Controlled Substances :: Part 1 - Schedules, Offenses, and Penalties :: § 16-13-29.1. Nonnarcotic Substances Excluded From Schedules of Controlled Substances". Justia Law. Archived from the original on 22 December 2023. Retrieved 22 December 2023.
  60. ^ "2010 Idaho Code :: Title 37 Food, Drugs, and Oil :: Chapter 27 Uniform Controlled Substances :: Article Ii :: 37-2713 Schedule V." Justia Law. Archived from the original on 22 December 2023. Retrieved 22 December 2023.
  61. ^ "2017 Kansas Statutes :: Chapter 65 Public Health :: Article 41 Controlled Substances :: 65-4113 Substances included in schedule V." Justia Law. Archived from the original on 22 December 2023. Retrieved 22 December 2023.
  62. ^ "2021 Rhode Island General Laws :: Title 21 - Food and Drugs :: Chapter 21-28 - Uniform Controlled Substances Act :: Section 21-28-2.08 - Contents of schedules". Justia Law. Archived from the original on 22 December 2023. Retrieved 22 December 2023.
  63. ^ Fornazzari L, Carlen PL, Kapur BM (November 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): 337–339. doi:10.1017/S0317167100036696. PMID 2877725.
  64. ^ Holler JM, Vorce SP, McDonough-Bender PC, Magluilo J, Solomon CJ, Levine B (January 2011). "A drug toxicity death involving propylhexedrine and mitragynine". Journal of Analytical Toxicology. 35 (1): 54–59. doi:10.1093/anatox/35.1.54. PMID 21219704.
  65. ^ a b Anderson ED (May 1970). "Propylhexedrine (Benzedrex) psychosis". The New Zealand Medical Journal. 71 (456): 302. PMID 5270979. S2CID 30786926.
  66. ^ Cooper D. ""Future Synthetic Drugs of Abuse"". Erowid. Drug Enforcement Administration. Archived from the original on 9 August 2023. Retrieved 9 August 2023.
  67. ^ Garriott JC (1975). "Editorial: Propylhexadrine - a new dangerous drug?". Clinical Toxicology. 8 (6): 665–666. doi:10.3109/15563657508990092. PMID 6189.
  68. ^ Curry B (5 September 1985). "Abuse of Potentially Fatal Nasal Inhaler Medication by Injection Called Widespread". LA Times. Archived from the original on 9 May 2021. Retrieved 7 September 2023.
  69. ^ Darcın AE, Dilbaz N, Okay IT (October 2010). "Barbexaclone abuse in a cannabis ex-user". Substance Abuse. 31 (4): 270–272. doi:10.1080/08897077.2010.514246. PMID 21038181. S2CID 7076881.
  70. ^ "Benzedrex Trademark of B.F. Ascher & Company Inc - Registration Number 0896775 - Serial Number 72340742". Justia. Archived from the original on 16 July 2023. Retrieved 16 July 2023.
  71. ^ Robertson V (17 February 2004). "Prince v. B.F. Ascher Company, Inc., 90 P.3d 1020 (Okla. Civ. App. 2004)". CaseText. Archived from the original on 16 July 2023. Retrieved 16 July 2023.
  72. ^ "B.F. Ascher marks 50th year". The Free Library. Chain Drug Review. 1 March 1999. Archived from the original on 9 August 2023. Retrieved 9 August 2023.
  73. ^ "Action in Respect of International Conventions on Narcotic Drugs and Psychotropic Substances" (PDF). World Health Organization. 24 November 1989. Archived from the original (PDF) on 29 October 2023. Retrieved 29 October 2023.
  74. ^ Angrist BM, Schweitzer JW, Gershon S, Friedhoff AJ (March 1970). "Mephentermine psychosis: misuse of the Wyamine inhaler". The American Journal of Psychiatry. 126 (9): 1315–1317. doi:10.1176/ajp.126.9.1315. PMID 5413209.
  75. ^ "Foundation Consumer Healthcare to Add Seven Over-the-Counter Brands to Expanding Portfolio of Healthcare Products" (PDF). Foundation Consumer Brands. Kelso & Company. 1 October 2020. Archived from the original (PDF) on 13 November 2023. Retrieved 13 November 2023.
  76. ^ Krueger HJ, Schwarz H (April 1965). "[Clinical Communication on the Therapy of Epilepsy With Maliasin]". Die Medizinische Welt. 14: 690–692. PMID 14276849.
  77. ^ "MALIASIN Trademark - Registration Number 0797076 - Serial Number 72213021". Justia. Archived from the original on 16 July 2023. Retrieved 16 July 2023.
  78. ^ Serracchiani D (31 January 2011). "Parliamentary question | Maliasin | P-001035/2011 | European Parliament". European Parliament. Archived from the original on 16 July 2023. Retrieved 16 July 2023.
  79. ^ Hofer R, Locker A (April 1958). "[Therapeutic experiences with the appetite depressant eventin]". Wiener Medizinische Wochenschrift. 108 (14): 304–306. PMID 13558159.
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