| Summary sheet: Phenmetrazine |
| Phenmetrazine | |||||||||||||||||||
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| Chemical Nomenclature | |||||||||||||||||||
| Common names | Preludin | ||||||||||||||||||
| Substitutive name | Phenmetrazine | ||||||||||||||||||
| Systematic name | 3-methyl-2-phenylmorpholine | ||||||||||||||||||
| Class Membership | |||||||||||||||||||
| Psychoactive class | Stimulant | ||||||||||||||||||
| Chemical class | Amphetamine | ||||||||||||||||||
| Routes of Administration | |||||||||||||||||||
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| Interactions | |||||||||||||||||||
Phenmetrazine (also known as Preludin among many others) is a phenylmorpholine stimulant substance of the substituted amphetamine chemical class. Although it produces classical stimulant effects which includes stimulation, focus & motivation enhancement, thought acceleration, wakefulness, and euphoria when administered, it has been uniquely distinguished as having been historically preferred by users over amphetamine and even methamphetamine, at least in Sweden.[1]
Phenmetrazine was first patented in Germany in 1952 by Boehringer-Ingelheim,[2][3] with some pharmacological data published in 1954.[4] It was the result of a search by Thomä and Wick for an anorectic drug without the side-effects of amphetamine.[5]
In clinical use, phenmetrazine produces less nervousness, hyperexcitability, euphoria and insomnia than drugs of the amphetamine family.[6] It tends not to increase heart rate as much as other stimulants. Due to the relative lack of side effects, one study found it well tolerated in children.[7]
Phenmetrazine was clinically used in Europe as an anorectic (weight-loss agent) in the 1950s. It was later withdrawn due to concerns over misuse and addiction stemming from widespread recreational use.[8] Prodrug Phendimetrazine was synthesized and is still in use today, use appears regulated internationally as under the Convention of Narcotic Substances, Phendimetrazine is a Schedule III controlled substance.[9] Today, phenmetrazine is no longer produced and although detection of use has been noted in some countries</ref>Choi H, Baeck S, Jang M, Lee S, Choi H, Chung H (February 2012). "Simultaneous analysis of psychotropic phenylalkylamines in oral fluid by GC-MS with automated SPE and its application to legal cases". Forensic Science International. 215 (1–3): 81–7. PMID 21377815, it appears to have been largely superseded by amphetamine in both its pharmaceutical and street forms as well as by its research chemical analog 3-fluorophenmetrazine (3-FPM).
Chemistry
Phenmetrazine is a synthetic molecule of the amphetamine family. Molecules of the amphetamine class contain a phenethylamine core featuring a phenyl ring bound to an amino (NH2) group through an ethyl chain with an additional methyl substitution at Rα. Amphetamines are alpha-methylated phenethylamines.
Phenmetrazine is comprised of an amphetamine skeleton that has been incorporated into a morpholine ring. At R2 of its chain, an oxygen group is bound -- this oxygen group is linked by an ethyl chain to the terminal amine of the amphetamine chain to form a morpholine group.
Phenmetrazine is the parent compound of the popular research chemical 3-fluorophenmetrazine.
Pharmacology
Phenmetrazine acts as a releasing agent of norepinephrine and dopamine with EC50 values of 50.4 ± 5.4 nM and 131 ± 11 nM, respectively.[10] It has negligible efficacy as a releaser of serotonin, with an EC50 value of only 7,765 ± 610 nM.[10] This accumulation of neurotransmitters in the synaptic cleft results in its euphoric and stimulating effects.
After an oral dose, about 70% of the drug is excreted from the body within 24 hours. About 19% of that is excreted as the unmetabolized drug and the rest as various metabolites.[11]
In trials performed on rats, it has been found that after subcutaneous administration of phenmetrazine, both optical isomers are equally effective in reducing food intake, but in oral administration the levo isomer is more effective. In terms of central stimulation, however, the dextro isomer is about 4 times as effective in both methods of administration.[12]
Below is a table showing phenmetrazine's potency for inducing release (EC50) of dopamine (DA), serotonin (5-HT) and noradrenaline (NE):
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[10] |
Subjective effects
Disclaimer: The effects listed below cite the Subjective Effect Index (SEI), an open research literature based on anecdotal user reports and the personal analyses of PsychonautWiki contributors. As a result, they should be viewed with a healthy degree of skepticism.
It is also worth noting that these effects will not necessarily occur in a predictable or reliable manner, although higher doses are more liable to induce the full spectrum of effects. Likewise, adverse effects become increasingly likely with higher doses and may include addiction, severe injury, or death ☠.
Physical effects 
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- Stimulation - In terms of its effects on the physical energy levels of the user, phenmetrazine is usually considered to be mildly to moderately energetic and stimulating in a fashion that is considerably weaker in comparison to that of traditional recreational stimulants such as amphetamine, MDMA or cocaine. This encourages physical activities such as performing chores and repetitive tasks which would otherwise be boring and strenuous physical activities.
- Increased heart rate[citation needed] - In comparison to other stimulants such as amphetamine or cocaine, phenmetrazine only has a mild effect on one's heart rate.
- Increased blood pressure[citation needed]
- Stamina enhancement
- Appetite suppression - The above components are also accompanied by a suppression of appetite which is usually much less intense in strength in comparison to the appetite suppression experienced with amphetamine or methamphetamine.
- Increased perspiration
- Dehydration
- Frequent urination
- Dry mouth
- Vasoconstriction [citation needed]
- Increased libido - Phenmetrazine has been reported to enhance sex drive and improve sexual performance.[citation needed]
- Pupil dilation
- Teeth grinding - This component can be considered to be less intense when compared with that of MDMA and many other stimulants.
Cognitive effects 
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- Anxiety
- Analysis enhancement
- Disinhibition - While phenmetrazine is often noted for its potential functional applications, higher doses can result in the kind of disinhibition seen in traditional stimulants like amphetamine or cocaine, leading to increased sociability.
- Cognitive euphoria - This component is much less intense than the euphoria experienced with other stimulants such as amphetamine, cocaine, or methamphetamine.
- Ego inflation
- Focus enhancement - This component is most effective at low to moderate doses as anything higher will usually impair concentration.
- Motivation enhancement - This component is experienced in a functional form even at moderate to high doses.
- Immersion enhancement
- Increased music appreciation
- Thought acceleration
- Time compression - This can be described as the experience of time speeding up and passing much quicker than it usually would when sober.
- Wakefulness
After effects 
- 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:
Experience reports
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
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This toxicity and harm potential section is a stub. As a result, it may contain incomplete or even dangerously wrong information! You can help by expanding upon or correcting it. |
The toxicity and long-term health effects of recreational phenmetrazine use do not seem to have been studied in any scientific context and the exact toxic dosage is unknown.[citation needed]
It is strongly recommended that one use harm reduction practices when using this substance.
Tolerance and addiction potential
As with other stimulants, the chronic use of phenmetrazine can be considered moderately addictive with a high potential for abuse and is capable of causing psychological dependence among certain users. When addiction has developed, cravings and withdrawal effects may occur if a person suddenly stops their usage.
Tolerance to many of the effects of phenmetrazine 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 - 2 weeks to be back at baseline (in the absence of further consumption). Phenmetrazine presents cross-tolerance with all dopaminergic stimulants, meaning that after the consumption of phenmetrazine all stimulants will have a reduced effect.
Dangerous interactions
Warning: Many psychoactive substances that are reasonably safe to use on their own can suddenly become dangerous and even life-threatening when combined with certain other substances. The following list provides some known dangerous interactions (although it is not guaranteed to include all of them).
Always conduct independent research (e.g. Google, DuckDuckGo, PubMed) to ensure that a combination of two or more substances is safe to consume. Some of the listed interactions have been sourced from TripSit.
- 25x-NBOMe & 25x-NBOH - 25x compounds are highly stimulating and physically straining. Combinations with Phenmetrazine should be strictly avoided due to the risk of excessive stimulation and heart strain. This can result in increased blood pressure, vasoconstriction, panic attacks, thought loops, seizures, and heart failure in extreme cases.
- Alcohol - Combining alcohol with stimulants can be dangerous due to the risk of accidental over-intoxication. Stimulants mask alcohol's depressant effects, which is what most people use to assess their degree of intoxication. Once the stimulant wears off, the depressant effects will be left unopposed, which can result in blackouts and severe respiratory depression. If mixing, the user should strictly limit themselves to only drinking a certain amount of alcohol per hour.
- DXM - Combinations with DXM should be avoided due to its inhibiting effects on serotonin and norepinephrine reuptake. There is an increased risk of panic attacks and hypertensive crisis, or serotonin syndrome with serotonin releasers (MDMA, methylone, mephedrone, etc.). Monitor blood pressure carefully and avoid strenuous physical activity.
- MDMA - Any neurotoxic effects of MDMA are likely to be increased when other stimulants are present. There is also a risk of excessive blood pressure and heart strain (cardiotoxicity).
- MXE - Some reports suggest combinations with MXE may dangerously increase blood pressure and increase the risk of mania and psychosis.
- Dissociatives - Both classes carry a risk of delusions, mania and psychosis, and these risk may be multiplied when combined.
- Stimulants - Phenmetrazine may be dangerous to combine with other stimulants like cocaine as they can increase one's heart rate and blood pressure to dangerous levels.
- Tramadol - Tramadol is known to lower the seizure threshold[13] and combinations with stimulants may further increase this risk.
- MDMA - The neurotoxic effects of MDMA may be increased when combined with amphetamines and related compounds like the phenmetrazines.[citation needed]
- MAOIs - This combination may increase the amount of neurotransmitters such as dopamine to dangerous or even fatal levels. Examples include syrian rue, banisteriopsis caapi, and some antidepressants.[14]
- Cocaine - This combination may increase strain on the heart to dangerous levels.[citation needed]
Legal status
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This legality section is a stub. As such, it may contain incomplete or wrong information. You can help by expanding it. |
See also
External links
References
- ↑ Brecher EM. "The Swedish Experience"
- ↑ Albert Boehringer; Ernst Boehringer. Improvements in or relating to the preparation of substituted morpholines. GB773780.
- ↑ US Patent 2835669 - Process for the Production of Substituted Morpholines
- ↑ Thomä, O & Wick, H (1954). "Über einige Tetrahydro-1,4-oxazine mit sympathicomimetischen Eigenschaften". Arch. Exp. Pathol. Pharmakol. 222: 540.
- ↑ https://link.springer.com/article/10.1007/BF00246905
- ↑ "Phenmetrazine Hydrochloride". J. Am. Med. Assoc. 163 (5): 357. 1957.
- ↑ Martel, Antonio (1957). "Preludin (Phenmetrazine) in the Treatment of Obesity". Can. Med. Assoc. J. 76 (2): 117–20. PMC 1823494 Freely accessible. PMID 13383418.
- ↑ Kalant, Oriana Josseau (1966). The Amphetamines: Toxicity and Addiction. ISBN 0-398-02511-8.
- ↑ https://web.archive.org/web/20120831222336/http://www.incb.org/pdf/e/list/green.pdf
- ↑ 10.0 10.1 10.2 Rothman RB, Baumann MH (2006). "Therapeutic potential of monoamine transporter substrates". Current Topics in Medicinal Chemistry. 6 (17): 1845–59. PMID 17017961. https://doi.org/10.2174/156802606778249766.
- ↑ Anthony C Moffat, M David Osselton and Brian Widdop. Clarke's Analysis of Drugs and Poisons. ISBN 0-85369-473-7.
- ↑ Engelhardt, A (1961). "Studies of the Mechanism of the Anti-Appetite Action of Phenmetrazine". Biochem. Pharmacol. 8 (1): 100. doi:10.1016/0006-2952(61)90520-2.
- ↑ 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. doi:10.1007/BF03161089. eISSN 1937-6995. ISSN 1556-9039. OCLC 163567183.
- ↑ Gillman, P. K. (2005). "Monoamine oxidase inhibitors, opioid analgesics and serotonin toxicity". British Journal of Anaesthesia. 95 (4): 434–441. doi:10.1093/bja/aei210
. eISSN 1471-6771. ISSN 0007-0912. OCLC 01537271. PMID 16051647.