Tapentadol

Tapentadol (3-((1R,2R)-3-(dimethylamino)-1-ethyl-2-methylpropyl) phenol hydrochloride) is a non-racemic molecule. The molecular formula of Tapentadol is C14H23NO.HCl. It was first synthesized in USA and marketed by Ortho-McNeil-Janssen Pharmaceuticals; its trade name was Nucynta.^[2]

Tapentadol is similar in structure to both tramadol and dextropropoxyphene. Tapentadol has one cyclic ring, unlike tramadol which has two. The empirical formula of tapentadol is C₁₄H₂₃NO and has a molar mass of 221.339 grams per mole.^[3] Tapentadol has thefull IUPAC name: 3-[(2R,3R)-1-(dimethylamino)-2-methylpentan-3-yl]phenol.

Opioids exert their effects by binding to and activating the μ-opioid receptor. This occurs because opioids structurally mimic endogenous endorphins which are naturally found within the body and also work upon the μ-opioid receptor set. The way in which opioids structurally mimic these natural endorphins results in their euphoria, pain relief and anxiolytic effects. This is because endorphins are responsible for reducing pain, causing sleepiness, and feelings of pleasure. They can be released in response to pain, strenuous exercise, orgasm, or general excitement. Tapentadol has an oral bioavailability of about 32%. Tapentadol is metabolized by the Cytochrome P450 system in the liver and is excreted by the kidneys in urine as well as in feces. Unlike most opioids, tapentadol is also a norepinephrine reuptake inhibitor and also has weak serotonergic effects as well.^[4]

Tapentadol is an orally available, synthetic benzenoid that acts as an agonist for the mu-opioid receptor (MOR) and inhibits the reuptake of noradrenaline, with potential anti-nociceptive activity. Upon oral administration, tapentadol binds to the MOR which enhances MOR-mediated signaling, interferes with the sensation of pain and results in an analgesic effect. Tapentadol also inhibits the reuptake of noradrenaline, which increases the levels of noradrenaline (NA), activates the inhibitory alpha-2 receptors and results in an analgesic effect.^[5]

Tapentadol and its metabolites are excreted almost exclusively (99%) via the kidneys. Approximately 70% (55% O-glucuronide and 15% sulfate of tapentadol) is excreted in conjugated form. A total of 3% of drug was excreted in urine as unchanged drug.^[6]

Disclaimer: The effects listed below cite the Subjective Effect Index (SEI), a research literature based on anecdotal reports and the personal experiences of PsychonautWiki contributors. As a result, they should be regarded with a healthy degree of skepticism. It is 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 much more likely with higher doses and may include addiction, serious injury, or death.

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:

• Erowid Experience Vaults: Tapentadol

Tapentadol has a low toxicity relative to dose. As with all opioids, long-term effects can vary but can include diminished libido, apathy and memory loss. It is also potentially lethal when mixed with depressants like alcohol or benzodiazepines and generally has a wider range of substances which it is dangerous to combine with in comparison to other opioids. Tapentadol is known to lower the seizure threshold. It should not be taken during benzodiazepine withdrawals as this can potentially cause seizures.

It is strongly recommended that one use harm reduction practices when using this drug.

Tolerance and addiction potential

As with other opioids, the chronic use of tapentadol 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 symptoms may occur if a person suddenly stops their usage.

Tolerance to many of the effects of tapentadol develops with prolonged and repeated use. The rate at which this occurs develops at different rates for different effects, with tolerance to the constipation-inducing effects developing particularly slowly for instance. 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). Tapentadol presents cross-tolerance with all other opioids, meaning that after the consumption of tapentadol all opioids will have a reduced effect.

Dangerous interactions

Although many psychoactive substances are reasonably safe to use on their own, they can suddenly become dangerous or even life-threatening when combined with other substances. The following list includes some known dangerous combinations (although it is not 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 of the listed interactions have been sourced from TripSit.

• Alcohol - Both substances potentiate the ataxia and sedation caused by the other and can lead to unexpected loss of consciousness at high doses. Place affected patients in the recovery position to prevent vomit aspiration from excess. Memory blackouts are likely
• Amphetamines - Stimulants increase respiration rate which allows for a higher dose of opiates than would otherwise be used. If the stimulant wears off first then the opiate may overcome the user and cause respiratory arrest.
• Benzodiazepines - Central nervous system and/or respiratory-depressant effects may be additively or synergistically present. The two substances potentiate each other strongly and unpredictably, very rapidly leading to unconsciousness. While unconscious, vomit aspiration is a risk if not placed in the recovery position blackouts/memory loss likely.
• Cocaine - Stimulants increase respiration rate, which allows for a higher dose of opiates than would otherwise be used. If the stimulant wears off first then the opiate may overcome the patient and cause respiratory arrest.
• DXM - Generally considered to be toxic. CNS depression, difficulty breathing, heart issues, and liver toxicity have been observed. Additionally if one takes DXM, their tolerance of opiates goes down slightly, thus causing additional synergistic effects.
• GHB/GBL - The two substances potentiate each other strongly and unpredictably, very rapidly leading to unconsciousness. While unconscious, vomit aspiration is a risk if not placed in the recovery position
• Ketamine - Both substances bring a risk of vomiting and unconsciousness. If the user falls unconscious while under the influence there is a severe risk of vomit aspiration if they are not placed in the recovery position.
• MAOIs - Coadministration of monoamine oxidase inhibitors (MAOIs) with certain opioids has been associated with rare reports of severe adverse reactions. There appear to be two types of interaction, an excitatory and a depressive one. Symptoms of the excitatory reaction may include agitation, headache, diaphoresis, hyperpyrexia, flushing, shivering, myoclonus, rigidity, tremor, diarrhea, hypertension, tachycardia, seizures, and coma. Death has occurred in some cases.
• MXE - MXE can potentiate the effects of opioids but also increases the risk of respiratory depression and organ toxicity.
• Nitrous - Both substances potentiate the ataxia and sedation caused by the other and can lead to unexpected loss of consciousness at high doses. While unconscious, vomit aspiration is a risk if not placed in the recovery position. Memory blackouts are common.
• PCP - PCP may reduce opioid tolerance, increasing the risk of overdose.
• Tramadol - Increased risk of seizures. Tramadol itself is known to induce seizures and it may have additive effects on seizure threshold with other opioids. Central nervous system- and/or respiratory-depressant effects may be additively or synergistically present.
• Grapefruit - While grapefruit is not psychoactive, it may affect the metabolism of certain opioids. Tramadol, oxycodone, and fentanyl are all primarily metabolized by the enzyme CYP3A4, which is potently inhibited by grapefruit juice^[7]. This may cause the drug to take longer to clear from the body. it may increase toxicity with repeated doses. Methadone may also be affected^[7]. Codeine and hydrocodone are metabolized by CYP2D6. People who are on medicines that inhibit CYP2D6, or that lack the enzyme due to a genetic mutation will not respond to codeine as it can not be metabolized into its active product: morphine.

Serotonin syndrome risk

Combinations with the following substances can cause dangerously high serotonin levels. Serotonin syndrome requires immediate medical attention and can be fatal if left untreated.

• MAOIs - Such as banisteriopsis caapi, syrian rue, phenelzine, selegiline, and moclobemide.^[8]
• Serotonin releasers - Such as MDMA, 4-FA, methamphetamine, methylone and αMT.
• SSRIs - Such as citalopram and sertraline
• SNRIs - Such as tramadol and venlafaxine
• 5-HTP

• Germany: Tapentadol is a controlled substance under Anlage III of the BtMG. It can only be prescribed on a narcotic prescription form.^[9]
• Switzerland: Tapentadol is a controlled substance specifically named under Verzeichnis A. Medicinal use is permitted.^[10]
• United Kingdom: Tapentadol is a Class A, Schedule 2 drug in the United Kingdom.^[11]
• United States: Tapentadol is a Schedule II Controlled Substance.^[12]

• Responsible use
• Opioid
• Tramadol
• Fentanyl
• O-Desmethyltramadol

• Tapentadol (Wikipedia)
• Tapentadol (Isomer Design)