|Summary sheet: HDEP-28|
MDEP-28 (there is no informal name for it yet) is synthetic stimulant of the piperidine chemical class that produces stimulating, motivating, and focus enhancing effects when administered. It is a structural analog of the widely-prescribed ADHD medication methylphenidate and is reported to produce near identical cognitive and physical effects, albeit with less of a euphoric "rush" component and a drawn-out duration of action, properties that many find preferable for use as a study-aid or productivity enhancer. Depending on the ROA the time of action is variable. Snorting common doses can feel similar to cocaine, while swallowing larger doses procuces effecs similar to MDMA.
MDEP-28 has never been studies scientifically, therefore it is advised to follow hardm reduction practices.
MDEP-28has an extremely short history of recreational use in human and has yet to be documented being sold on the streets. It was initially released following the banning of ethylphenidate, which on April 2012 became illegal in the United Kingdom following a temporary-then-permanent blanket ban. Shortly after, it became made available for sale on the online gray market as a research chemical for global distribution.
As of 2017, MDEP-28continues to remain available and ambiguously legal in many parts of the world, distributed almost exclusively by online research chemical vendors.
- 1 Chemistry
- 2 Pharmacology
- 3 Subjective effects
- 4 Toxicity and harm potential
- 5 Legality
- 6 See also
- 7 External links
- 8 Literature
- 9 References
Isopropylphenidate is a synthetic molecule of the substituted phenethylamine and piperidine classes. It contains a phenethylamine core featuring a phenyl ring bound to an amino (NH2) group via an ethyl chain. It is structurally similar to amphetamine, featuring a substitution at Rα which is then incorporated into a piperidine ring ending at the terminal amine of the phenethylamine chain. Additionally, it contains an isopropyl acetate bound to R2 of its molecular structure, a noticeable departure from methylphenidate, which contains a methyl group in this position.
Isopropylphenidate structurally diverges from ethylphenidate and methylphenidate by the length of the carbon chain on their acetate group. Iso- regards the side chain of one carbon atom branching into two bound methyl groups, phen- indicates the phenyl ring, id- is contracted from the piperidine ring, and -ate indicates the acetate group. Isopropylphenidate is a chiral compound, and has been documented as being produced as a racemic mixture and exclusively as either of its enantiomers.
No formal in vivo human studies carried out using isopropylphenidate; however in vivo rat studies and in vitro studies have been performed to observe the stimulatory effects in rats, and evaluate the monoamine transporter binding affinities and affinities for various hydrolytic enzymes respectively. The results of these studies suggest that isopropylphenidate has a very similar pharmacology to its parent compound methylphenidate, with the notable differences between the two substances being isopropylphenidate displaying significantly less activity as a norepinephrine reuptake inhibitor and the CES1 hydrolytic enzyme, which is exclusively responsible for hydrolysing both substances to ritalinic acid, having an 8 times lower affinity for isopropylphenidate compared to methylphenidate.
These differences result in the substance having more notable dopaminergic activity than adrenergic activity compared to methylphenidate at equivalent effective dosages, and in the substance having a longer duration than methylphenidate and a greater potency than methylphenidate at a given dosage. The greater potency of isopropylphenidate compared to methylphenidate is most significant with oral administration as the difference in potency is a result of the lower affinity of CES1 increasing the bioavailability of isopropylphenidate compared to methylphenidate, which is notably low for methylphenidate when administered orally due to first-pass metabolism in the liver by CES1.
Despite the notable differences between the two substances, isopropylphenidate is still thought to act primarily as both a dopamine reuptake inhibitor and a norepinephrine reuptake inhibitor, meaning that it effectively boosts the levels of the norepinephrine and dopamine neurotransmitters in the brain by binding to and partially blocking the transporter proteins that normally remove those monoamines from the synaptic cleft. This allows dopamine and norepinephrine to accumulate within the brain, resulting in stimulatory effects.
Disclaimer: The effects listed below cite the Subjective Effect Index (SEI), a literature based on anecdotal reports and the personal experiences of PsychonautWiki contributors. As a result, they should be treated 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 are more likely to induce the full spectrum of effects. Likewise, adverse effects become much more likely with higher doses and may include serious injury or death.
The physical effects of isopropylphenidate are often described as less uncomfortable and euphoric than ethylphenidate. They can be broken down into several components which progressively intensify proportional to dosage. These are described below and generally include:
- Stimulation - Isopropylphenidate is usually considered to be energetic and stimulating in a fashion that is distinct but much weaker than that of amphetamine or methamphetamine and stronger than that of modafinil and caffeine. At lower to moderate doses, it encourages general productivity, but at higher dosages it encourages physical activities such as dancing, socializing, running, or cleaning. The particular style of stimulation which isopropylphenidate presents can be described as forced. This means that at higher doses, it becomes difficult or impossible to keep still as jaw clenching, involuntarily bodily shakes and vibrations become present, resulting in unsteadiness of the hands, shaking of the entire body and a general loss of motor control.
- Dry mouth
- Appetite suppression
- Increased heart rate
- Mouth numbing - When administered sublingually a long-lasting numbing sensation has been reported to occur.
- Teeth grinding - This component can be considered to be less intense when compared with that of MDMA.
- 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:
The cognitive effects of isopropylphenidate can be broken down into several components which progressively intensify proportional to dosage. The general headspace of isopropylphenidate is described by many as one of mental stimulation, increased focus, and manageable euphoria. It contains a large number of typical stimulant cognitive effects. Although negative side effects are usually mild at low to moderate doses, they become increasingly likely to manifest themselves with higher amounts or extended usage. This particularly holds true during the offset of the experience.
The most prominent of these cognitive effects generally include:
- Analysis enhancement
- Focus enhancement - This component is most effective at low to moderate doses as anything higher will usually impair concentration.
- Motivation enhancement
- Stamina enhancement
- Thought acceleration
- Thought connectivity
- Cognitive euphoria - The euphoric rush associated with isopropylphenidate use (as a result of dopamine reuptake inhibition) is very short-lived and compulsive, vaguely similar to that of cocaine.
- Increased music appreciation
- Increased libido - This component is generally considered mild compared to that of other stimulants.
- Irritability - At higher dosage ranges this is often felt during the peak of the experience in addition to during the offset. This can potentially be attributed to the unusually high dopaminergic activity it displays relative to noradrenergic activity.
- Time distortion - This can be described as the experience of time speeding up and passing much quicker than it would while sober.
- Compulsive redosing - This can be attributed to the mild-to-moderate euphoric rush and relatively short half-life of isopropylphenidate possesses, and is especially prominent when it is insufflated. Those who wish to use it for productivity purposes are advised to only take low to moderate doses strictly through oral administration. insufflation can amplify the urge to redose. Many users report that the compulsive redosing aspects of isopropylphenidate are far more tame and controllable than the majority of research chemical stimulants, such as 4F-MPH, a-PHP or Hexen, likely due to the absence of a pronounced rush and an extended onset.
There are currently anecdotal reports which describe the effects of this compound within our experience index.
- Experience:30mg Isopropylphenidate - IPPH As A Study Aid
- Experience:37mg Isopropylphenidate - Getting Shit Done With Isopropylphenidate
Additional experience reports can be found here:
Toxicity and harm potential
The toxicity and long-term health effects of recreational isopropylphenidate use do not seem to have been studied in any scientific context and the exact toxic dosage is unknown. This is because isopropylphenidate has very little history of human usage. Anecdotal evidence from people who have tried isopropylphenidate within the community suggests that there do not seem to be any negative health effects attributed to simply trying this drug at low to moderate doses by itself and using it sparingly (but nothing can be completely guaranteed). It is strongly recommended that one use harm reduction practices when using this drug.
Tolerance and addiction potential
As with other stimulants, the chronic use of isopropylphenidate 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 isopropylphenidate 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). Isopropylphenidate presents cross-tolerance with all dopaminergic stimulants, meaning that after the consumption of isopropylphenidate all stimulants will have a reduced effect.
Abuse of compounds within the stimulant 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.
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 - HDEP-28 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, and some antidepressants.
- MDMA - The neurotoxic effects of MDMA may be increased when combined with other stimulants.
- Cocaine - This combination may increase strain on the heart.
This legality section is a stub.
As such, it may contain incomplete or wrong information. You can help by expanding it.
- Germany: Isopropylphenidate is controlled under the NpSG, as it is a derivative of 2-Phenethylamine. Production and sale is illegal. Possession and import, although illegal, is not penalized if intended for self-consumption.
- United Kingdom - Isopropylphenidate is a class B drug in the UK as of 31st May 2017 and is illegal to possess, produce or supply. 
- Markowitz, J. S., Zhu, H., & Patrick, K. S. (2013). Isopropylphenidate: An Ester Homolog of Methylphenidate with Sustained and Selective Dopaminergic Activity and Reduced Drug Interaction Liability. Journal of Child and Adolescent Psychopharmacology, 23(10), 648-654. https://doi.org/10.1089/cap.2013.0074
- John S. Markowitz; Kennerly S. Patrick; Haojie Zhu (Sep 27, 2012). "Patent US20120245201 - Isopropylphenidate for Treatment of Attention-Deficit/Hyperactivity Disorder and Fatigue-Related Disorders and Conditions". Retrieved 15 August 2014.
- Lachman, L., & Malspeis, L. (1962). U.S. Patent No. 3060089. Washington, DC: U.S. Patent and Trademark Office. Therapeutic lower alkyl esters of alpha-phenyl-alpha-piperidyl-(2)-acetic acid
- Cite error: Invalid
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- Portoghese, P. S., & Malspeis, L. (1961), Relative hydrolytic rates of certain alkyl (b) dl-α-(2-piperidyl)-phenylacetates. J. Pharm. Sci., 50: 494–501. https://doi.org/10.1002/jps.2600500611
- Kimko, H. C., Cross, J. T., & Abernethy, D. R. (1999). Pharmacokinetics and Clinical Effectiveness of Methylphenidate. Clinical Pharmacokinetics, 37(6), 457-470. https://doi.org/10.2165/00003088-199937060-00002
- Shoptaw, S. J., Kao, U., & Ling, W. (2009). Treatment for amphetamine psychosis. The Cochrane Library. https://doi.org/10.1002/14651858.CD003026.pub3
- Hofmann FG (1983). A Handbook on Drug and Alcohol Abuse: The Biomedical Aspects (2nd ed.). New York: Oxford University Press. p. 329. ISBN 9780195030570.
- 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. doi: . eISSN 1471-6771. ISSN 0007-0912. OCLC 01537271. PMID 16051647.
- The Misuse of Drugs Act 1971 (Amendment) Order 2017 (Legislation.gov.uk) | http://www.legislation.gov.uk/uksi/2017/634/made