|Summary sheet: 4-Methylaminorex|
|Common names||4-Methylaminorex, 4-MAR, 4-MAX, U4Euh, Ice|
|Chemical class||Substituted aminorex|
|Routes of Administration|
4-Methylaminorex (4-MAR, 4-MAX) is a stimulant drug of the 2-amino-5-aryloxazoline class that was first synthesized in 1960 by McNeil Laboratories. It is also known by its street names "U4Euh" ("Euphoria") and "Ice". It is banned in many countries as a stimulant.
4-Methylaminorex has effects comparable to methamphetamine but with a longer duration.
- 1 Chemistry
- 2 Pharmacology
- 3 Subjective effects
- 4 Toxicity and harm potential
- 5 Legal issues
- 6 See also
- 7 External links
- 8 References
4-Methylaminorex exists as four stereoisomers - (±)-cis and (±)-trans. The (±)-cis isomers are the form used recreationally. The (±)-cis isomers [racemate (1:1-mixture) of the (4R,5S)-isomer and the enantiomeric (4S,5R)-isomer] generally synthesized from dl-phenylpropanolamine in one step by cyclization with cyanogen bromide (sometimes prepared in situ by reacting sodium cyanide with bromine). Alternate synthesis routes generally involve more steps, such as replacing cyanogen bromide with sodium or potassium cyanate to form an intermediate and then reacting it with concentrated hydrochloric acid. A method reported in microgram replaced the need for a separate addition of hydrochloric acid by starting with the hydrochloride salt of the dl-phenylpropanolamine but side-products are noted. The (±)-trans isomers [racemate (1:1-mixture) of the (4S,5S)-isomer and the enantiomeric (4R,5R)-isomer] are synthesized in the same manner above but dl-norephedrine is used as the starting material instead. The cyanate reaction proceeds differently from the cyanogen bromide and transforms norephedrine into trans-4-methylaminorex instead. The cyanogen bromide, by comparison, transformed norephedrine into the cis isomer and norpseudoephedrine into the trans isomers of the final product.
It produces long-lasting effects, generally up to 16 hours in duration if taken orally and up to 12 hours if smoked or insufflated. Large doses have been reported anecdotally to last up to 36 hours. The effects are stimulant in nature, producing euphoria, an increase in attention, and increased cognition. Anecdotally, it has been reported to produce effects similar to nootropics, however, there is no research to support the claim that it is any different or more effective than other psychostimulants in this respect. Moreover, 4-methylaminorex does not have the established safety profile of widely used clinical psychostimulants such as methylphenidate and dextroamphetamine.
3-FA is considered to be a potent and complex stimulant with mild entactogenic undertones when compared to other substances its class, like 4-FA. However, it does not have the productivity and focus-enhancing effects often claimed by users of 2-FA or 2-FMA which has had the effect of limiting its appeal.
Disclaimer: The effects listed below cite the Subjective Effect Index (SEI), a literature which relies on collected anecdotal reports and the personal experiences of PsychonautWiki contributors. As a result, they should be taken with a healthy amount of skepticism. It is worth noting that these effects will not necessarily occur in a consistent or reliable manner, although higher doses (common+) are more likely to induce the full spectrum of reported effects. Likewise, adverse effects become much more likely with higher doses and may include serious injury or death.
- Tactile enhancement -
- Physical euphoria
- Appetite suppression
- Increased heart rate
- Increased perspiration
- Teeth grinding
- Cognitive euphoria
- Thought acceleration
- Focus enhancement
- Anxiety suppression
- Analysis enhancement
- Motivation enhancement
- Compulsive redosing
- Increased music appreciation
- Time distortion
The effects which occur during the offset of a stimulant experience generally feel negative and uncomfortable in comparison to the effects which occurred during its peak. This is often referred to as a "comedown" and occurs because of neurotransmitter depletion. Its effects commonly include:
- Cognitive fatigue
- Motivation suppression
- Thought deceleration
There are currently no anecdotal reports which describe the effects of this compound within our experience index. Additional experience reports can be found here:
Toxicity and harm potential
There has been one reported death due to 4-methylaminorex and diazepam. Concentrations of 4-methylaminorex were: in blood 21.3 mg/L; in urine 12.3 mg/L. Diazepam concentration in blood was 0.8 mg/L. One rat study has studied excretion of 4-methylaminorex in urine: "The concentration of trans-4-methylaminorex in rat urine following four injections of the trans-4S,5S isomer (5 mg/kg i.p each, at intervals of 12 h in 2 days, as measured quantitatively by GC/MS" The same study has studied pharmacokinetics and tissue distribution of the stereoisomers of 4-methylaminorex in rats.
"Pulmonary hypertension has been associated with ingestion of the appetite suppressant aminorex. A similar compound, 4-methylaminorex was discovered on the property of three individuals with diagnoses of pulmonary hypertension."
Tolerance and addiction potential
As with other stimulants, the chronic use of 4-Methylaminorex can be considered moderately addictive with a high potential for abuse and is capable of causing psychological dependence among a certain population of users. When dependence or addiction has developed, cravings and withdrawal effects may occur if a person suddenly stops their usage.
Tolerance to many of the effects of 4-Methylaminorex develops with prolonged and repeated use. This results in users having to administer increasingly large doses to achieve the same effects. After that, it takes about 3 - 7 days for the tolerance to be reduced to half and 1 - 10 days to be back at baseline (in the absence of further consumption). 4-Methylaminorex presents cross-tolerance with all dopaminergic stimulants, meaning that after the consumption of 4-Methylaminorex all stimulants will have a reduced effect (especially including atypical stimulants one might not expect, like MDMA due to its reliance on dopamine and norepinephrine to exert its full euphoric effect).
Given its close equipotency to methamphetamine, it likely shares similar toxicity profiles, though this has yet to be scientifically validated.
Abuse of compounds within the amphetamine chemical class at high dosages for prolonged periods of time can potentially result in a stimulant psychosis that may present with a variety of symptoms (e.g., paranoia, hallucinations, or delusions). A review on treatment for amphetamine, dextroamphetamine, and methamphetamine abuse-induced psychosis states that about 5–15% of users fail to recover completely. The same review asserts that, based upon at least one trial, antipsychotic medications effectively resolve the symptoms of acute amphetamine psychosis. Psychosis very rarely arises from therapeutic use.
Although many psychoactive substances are reasonably safe to use on their own, they can quickly become dangerous or even life-threatening when combined with other substances. The list below includes some known dangerous combinations (although it cannot be guaranteed to include all of them). Independent research (e.g. Google, DuckDuckGo) should always be conducted to ensure that a combination of two or more substances is safe to consume. Some interactions listed have been sourced from TripSit.
- 25x-NBOMe & 25x-NBOH - Members of the 25x family are highly stimulating and physically straining. Combinations with stimulants should be avoided due to the risk of excessive stimulation. This can result in panic attacks, thought loops, seizures, increased blood pressure, vasoconstriction, and heart failure in extreme cases.
- Alcohol - Alcohol can be dangerous to combine with stimulants due to the risk of accidental over-intoxication. Stimulants mask the sedative effects of alcohol, which is the main factor people use to assess their degree of intoxication. Once the stimulant wears off, the depressant effects of alcohol are left unopposed, which can result in blackouts and respiratory depression. If combined, one should strictly limit themselves to only drinking a certain amount of alcohol per hour.
- DXM - Combinations with DXM should be handled with extreme care due to DXM's effects on serotonin and norepinephrine reuptake. This can lead to panic attacks, hypertensive crisis, or serotonin syndrome with stimulants that increase levels of serotonin (MDMA, methylone, mephedrone, etc.). Monitor blood pressure carefully and avoid strenuous physical activity.
- MDMA - The neurotoxic effects of MDMA may be increased when combined with other stimulants. There is also a risk of excessive heart strain.
- MXE - Combinations with MXE may dangerously elevate blood pressure and increase the risk of psychosis.
- Stimulants - 4-Methylaminorex can be potentially dangerous in combination with other stimulants as they can increase one's heart rate and blood pressure to dangerous levels.
- Cocaine - This combination may increase strain on the heart.
- Tramadol - Tramadol lowers the seizure threshold. Combinations with stimulants may further increase this risk.
- MAOIs - This combination may increase the amount of neurotransmitters such as dopamine to dangerous or even fatal levels. Examples include syrian rue, banisteriopsis caapi, 2C-T-2, 2C-T-7, αMT, and some antidepressants.
In Australia, 4-Methylaminorex is listed as Schedule 9, making it legal only for scientific and medical research.
In Canada, 4-Methylaminorex is listed as Schedule III.
In the United Kingdom, 4-Methylaminorex is listed as Class A.
In the United States, (±)-cis-4-methylaminorex was placed in Schedule I of the Controlled Substances Act shortly after its emergence as a recreational drug in the mid-1980s. Manufacturing the trans isomer required a different process than those encountered when the substance was first scheduled, and was believed less potent than the cis isomer with a much lower abuse potential. However, studies revealing the abuse potential of the 'trans' isomer, coupled with the development of new clandestine synthetic methods that would produce the trans created a potential loophole in the law, which covered only the 'cis' isomer. To clarify the situation, the US Drug Enforcement Administration published a paper in its DEA Microgram Journal, regarding interpretation of the relevant statutory law as it relates to the status of trans-4-methylaminorex. In summary, according to this non-legally binding decision, trans-4-methylaminorex is not currently a controlled substance, but a potential analogue. In fact, the report explicitly states:
The United States [Drug Enforcement Administration] has the following opinion on the legality of the positional isomer "trans"-4-methylaminorex, which, unlike its 'cis' isomer was never placed in any schedule under the Controlled Substances Act.
However, the opinion does say that the agency considers the substance a potential controlled substance analogue, making the substance identical to a Schedule I substance if intended for human consumption, according to the Federal Analogue Act. The report gives an account of a successful conviction under the Federal Analogue Act of an offense involving the trans isomer.
"2-Amino-4-methyl-5-phenyl-2-oxazoline (4-methylaminorex)" and "any material, compound, mixture, or preparation that contains any quantity of" it "or that contains any of [its] salts, isomers, including optical, positional, or geometric isomers, and salts of isomers, if the existence of such salts, isomers, and salts of isomers is possible" is a Schedule I controlled substance in the state of Florida making it illegal to buy, sell, or possess in Florida.
- 2-amino-5-aryloxazoline compositions and methods of using same | https://www.google.com/patents/US3278382
- A fatality involving U4Euh, a cyclic derivative of phenylpropanolamine. | https://www.ncbi.nlm.nih.gov/pubmed/3373171
- Detection and assay of cis- and trans-isomers of 4-methylaminorex in urine, plasma and tissue samples. | https://www.ncbi.nlm.nih.gov/pubmed/11516888
- Treatment for amphetamine psychosis | 
- Treatment for amphetamine psychosis | 
- Hofmann FG (1983). A Handbook on Drug and Alcohol Abuse: The Biomedical Aspects (2nd ed.). New York: Oxford University Press. p. 329. ISBN 9780195030570.
- Treatment for amphetamine psychosis | 
- Stimulant Misuse: Strategies to Manage a Growing Problem | http://www.acha.org/prof_dev/ADHD_docs/ADHD_PDprogram_Article2.pdf
- Talaie, H., Panahandeh, R., Fayaznouri, M. R., Asadi, Z., & Abdollahi, M. (2009). Dose-independent occurrence of seizure with tramadol. Journal of Medical Toxicology, 5(2), 63-67. https://doi.org/10.1007/BF03161089
- Gillman, P. K. (2005). Monoamine oxidase inhibitors, opioid analgesics and serotonin toxicity. British Journal of Anaesthesia, 95(4), 434-441. https://doi.org/10.1093/bja/aei210
- "Poisons Standard 2009". Retrieved 2009-09-02.
- "Controlled Drugs and Substances Act". Retrieved 2009-09-02.
- "Bijlage 1 Lijst I Opiumwetmiddelen". Archived from the original on 2009-06-25. Retrieved 2009-09-02.
- "LIST OF DRUGS CURRENTLY CONTROLLED UNDER CLASS A" (PDF). Retrieved 2009-09-02.
- "Section 1308.11 Schedule I". Archived from the original on 27 August 2009. Retrieved 2009-09-02.
- Synthesis of trans-4-Methylaminorex from Norephedrine and Potassium Cyanate (DEA Microgram Journal)
- Florida Statutes - Chapter 893 - DRUG ABUSE PREVENTION AND CONTROL