|Summary sheet: Isopropylphenidate|
|Common names||Isopropylphenidate, IPH, IPPH|
|Systematic name||Propan-2-yl 2-phenyl-2-(piperidin-2-yl)acetate|
|Routes of Administration|
Isopropylphenidate (also known as IPH, IPPH, IPD and IPPD) is novel lesser-known stimulant of the phenidate chemical class. It is a structural analog of the widely-prescribed ADHD medication methylphenidate. It is a norepinephrine-dopamine reuptake inhibitor (NDRI).
Isopropylphenidate has been investigated for its potential use as a replacement for methylphenidate in the treatment of ADHD and related disorders. One study found that it displayed the same basic activity as a norepinephrine-dopamine reuptake inhibitor (NDRI), possessing, along with both methylphenidate and ethylphenidate, an appreciably high affinity for the dopamine transporter and effects on its cellular reuptake. It displayed comparably minor effects on norepinephrine, however, which was theorized to mean it may possess a more desirable safety and toxicity profile.
Subjective effects include stimulation, motivation enhancement, appetite suppression, and euphoria. Its cognitive and physical effects are reported to be similar to methylphenidate, albeit with less of a euphoric "rush" component and a drawn-out duration of action. These properties have led some to claim it may be preferable for use as a study-aid or productivity enhancer.
Isopropylphenidate has an extremely short history of recreational use in humans. It was initially released following the banning of ethylphenidate, which on April 2015 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 2022, isopropylphenidate continues to remain available and ambiguously legal in many parts of the world, distributed almost exclusively by online research chemical vendors.
Isopropylphenidate is a synthetic molecule of the substituted phenethylamine, substituted amphetamines and phenidate 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 Rβ 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.
Formal in-vivo human studies using isopropylphenidate have not been conducted. However, in vivo rat studies have found stimulatory effects; in vitro studies have evaluated 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), 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 ☠.
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.
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 Isopropylphenidate 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 - Isopropylphenidate 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 and 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.
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 (New Psychoactive Substances Act) as of November 26, 2016. Production and import with the aim to place it on the market, administration to another person and trading is punishable. Possession is illegal but not penalized.
- Switzerland: Isoprpoylphenidate is a controlled substance specifically named under Verzeichnis E.
- Turkey: Isopropylphenidate is illegal in Turkey as of February 2016.
- United Kingdom: Isopropylphenidate is a class B drug in the UK as of 31st May 2017 and is illegal to possess, produce or supply. 
- Canada: Isopropylphenidate is a Schedule III drug in Canada. 
- 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.
- ↑ 1.0 1.1 Markowitz, J. S., Patrick, K. S., Zhu, H., Isopropylphenidate for Treatment of Attention-Deficit/Hyperactivity Disorder and Fatigue-Related Disorders and Conditions
- ↑ 2.0 2.1 2.2 2.3 Markowitz, J. S., Zhu, H.-J., Patrick, K. S. (December 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. doi:10.1089/cap.2013.0074. ISSN 1044-5463.
- ↑ Leon, L., Louis, M., Therapeutic lower alkyl esters of alpha-phenyl-alpha-piperidyl-(2)-acetic acid
- ↑ Portoghese, P. S., Malspeis, L. (June 1961). "Relative Hydrolytic Rates of Certain Alkyl (b) dl-α-(2-Piperidyl)-phenylacetates". Journal of Pharmaceutical Sciences. 50 (6): 494–501. doi:10.1002/jps.2600500611. ISSN 0022-3549.
- ↑ Kimko, H. C., Cross, J. T., Abernethy, D. R. (1999). "Pharmacokinetics and Clinical Effectiveness of Methylphenidate:". Clinical Pharmacokinetics. 37 (6): 457–470. doi:10.2165/00003088-199937060-00002. ISSN 0312-5963.
- ↑ 6.0 6.1 6.2 Shoptaw, S. J., Kao, U., Ling, W. (21 January 2009). Cochrane Drugs and Alcohol Group, ed. "Treatment for amphetamine psychosis". Cochrane Database of Systematic Reviews. doi:10.1002/14651858.CD003026.pub3. ISSN 1465-1858.
- ↑ Hofmann, F. G. (1983). A handbook on drug and alcohol abuse: the biomedical aspects (2nd ed ed.). Oxford University Press. ISBN 9780195030563.
- ↑ 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.
- ↑ "Anlage NpSG" (in German). Bundesministerium der Justiz und für Verbraucherschutz. Retrieved December 24, 2019.
- ↑ "Gesetz zur Bekämpfung der Verbreitung neuer psychoaktiver Stoffe" (PDF) (in German). Bundesanzeiger Verlag. Retrieved December 24, 2019.
- ↑ "§ 4 NpSG" (in German). Bundesministerium der Justiz und für Verbraucherschutz. Retrieved December 24, 2019.
- ↑ "Verordnung des EDI über die Verzeichnisse der Betäubungsmittel, psychotropen Stoffe, Vorläuferstoffe und Hilfschemikalien" (in German). Bundeskanzlei [Federal Chancellery of Switzerland]. Retrieved January 1, 2020.
- ↑ "Karar Sayısı : 2016/8548" (PDF) (in Turkish). Resmi Gazete. Retrieved January 15, 2020.
- ↑ The Misuse of Drugs Act 1971 (Amendment) Order 2017
- ↑ "Controlled Drugs and Substances Act" (in English). Retrieved April 8, 2021.