New chemicals in the opioid section - W-15, W-18, MT-45, AH-7921,U-47700, Butyr-fentanyl, Acetyl-fentanyl, fentanyl

Just want to inform that RC scene has finally got some potent opioids to research with.
W-15 is 4 times the potency of morphine.
W-18 is 1000 times potency of morphine.

 W-18 ( 1-(4-Nitrophenylethyl)piperidylidene-2-(4-chlorophenyl)sulfonamide) is an interesting drug of a potency 10000x morphine that was discovered in 1981, the details of which were laid out in a patent (US4468403), and has virtually no history of human use.W-18

If you know a vendor who sells W-15 or W-18 on clear net please be so kind and let us know about it.

MT-45

IUPAC: 1-Cyclohexyl-4-(1^,2)-diphenylethyl)piperazine
MT-45 (IC-6) is an opioid analgesic drug invented in the 1970s by Dainippon Pharmaceutical Co^. It is chemically a 1-substituted-4-(1,2-diphenylethyl)piperazine derivative, which is structurally unrelated to most other opioid drugs. Racemic MT-45 has around 80% the potency of morphine, with almost all opioid activity residing in the (S) enantiomer (the opposite stereochemistry from the related drug lefetamine). It has been used as a lead compound from which a large family of potent opioid drugs have been developed, including full agonists, partial agonists, and antagonists at the three main opioid receptor subtypes.
Recreational use of MT-45 has been associated with hearing loss and unconsciousness.

^AH-7921

^{IUPAC: 3,4-dichloro-N-[(1-dimethylamino)cyclohexylmethyl]benzamide}

AH-7921 is an opioid analgesic drug selective for the µ-opioid receptor, having around 80% the potency of morphine when administered orally. It was discovered in the 1970s by a team at Allen and Hanburys.
Dosages have been reported to range from as little as 10 mg to around 200 mg or higher (for opioid-tolerant individuals). This would confirm the previous studies of AH-7921 being roughly 80% as potent as morphine^.

^U-47700 

^{IUPAC: trans-3,4-dichloro-N-(2-(dimethylamino)cyclohexyl)-N-methylbenzamide}

U-47700 is an opioid analgesic drug developed by a team at Upjohn in the 1970s. U-47700 was derived from an earlier opioid AH-7921. U-47700 is selective for the µ-opioid receptor, having around 7.5 x the potency of morphine in animal models^.
U-47700 is the result of a great deal of work elucidating the quantitative structure–activity relationship of the scaffold. The team looked for the key moieties which gave the greatest activity. Upjohn posted over a dozen patents on related compounds, each optimizing one moiety until they discovered that U-47700 was the most active.
U-47700 became the lead-compound of selective kappa ligands such as U-50488 and U-69,593, which share a very similar structure (a single methylene spacer difference). Its structure lead to other chemists experimenting with it to see if rigid analogues would retain activity.Although not used medically, the selective kappa ligands are used in research.
U-47700 has never been studied in humans, but would be expected to produce effects similar to those of other potent opioid agonists, including strong analgesia, sedation, euphoria, constipation, itching and respiratory depression which could be harmful or fatal. Tolerance and dependence would be expected to develop. Since affinity to kappa receptors has not been measured, it may also induce dysphoria and other unwanted side-effects but it’s 3DQSAR, make it this most unlikely. Its structure is somewhat similar to U-50488, a pure kappa agonist.

Butyr-fentanyl

IUPAC: N-(1-(2-phenylethyl)-4-piperidinyl)-N-phenylbutyramide
Butyr-fentanyl or butyrylfentanyl (not to be confused with 3-methylfentanyl) is a potent short-acting synthetic opioid analgesic drug. It is an analogue of fentanyl with around one quarter the potency of fentanyl. One of first mentions of this drug can be found in document written by The College on Problem of Drug Dependence, where it is mentioned as N-butyramide fentanyl analog. This document also states that the article describing its clinical effects (analgesic studies, m-, d-, k-Opioid receptor binding and in vitro measures of drug efficacy, antinociceptive and narcotic properties) was published in 1987. It is an agonist at mu opioid receptors.
Butyrfentanyl has no current legitimate clinical applications, but anecdotal reports indicate it may occasionally be surfacing on the grey-market as a recreational drug. This compound is not currently scheduled in the USA, but most likely falls under the purview of the federal and many state analogue drug laws. Butyrfentanyl is illegal in the United Kingdom owing to its chemical similarity to fentanyl.

Pharmacokinetics

Butyrfentanyl binds to the opioid receptor. During the studies of in vitro inhibition of specific [3H] fentanyl binding to the opioid receptor, the order of analogues was: (±)-cis-3-methylfentanyl > fentanyl = alpha-methylfentanyl > butyrylfentanyl > benzylfentanyl. The studies in inhibition studies on binding affinity achieved the same order of analogues. It means that butyrfentantyl is a less potent opioid-agonist than fentanyl. On the other side, during in vitro studies of cross-reactivity with the fentanyl antibody between fentanyl and the fentanyl analogs examined, revealed order: fentanyl = butyrylfentanyl > (±)-cis-3-methylfentanyl > benzylfentanyl > alpha-methylfentanyl.High cross-reactivity may be the effect of the shape of the molecule – the shape of butyrfentanyl is closest to the original fentanyl molecule, which makes it easy to bind by fentanyl antibodies.
The opioid receptor affinity of fentanyl and its analogs was determined from their inhibitory potency in a binding assay with [3H] fentanyl as the radioligand. The Ki value for butyrfentanyl was Ki=32 ± 4.1 nM. Comparing to fentanyl’s Ki (Ki=1.06 ± 0.15 nM), butyrfentanyl’s ability to displace [3H] fentanyl is low and it requires high concentrations of the drug.
During behavioral studies there was no evidence of causing adverse effects which accompany fentanyl’s use. Animals injected with 45μg/kg i.v. showed no behavioral responses in mice: straub tail, truncal and limbs rigidity, respiratory depression. These responses where observed in animals injected with 15 μg/kg fentanyl i.v.
Studies on urinary excretion revealed that almost all of the injected butyrfentanyl was excreted or metabolized within the first 3 h after injection, and only very low concentrations were still detectable after 3 h. Urinary concentrations of butyrylfentanyl from animals injected with 15 μg/kg and 45 μg/kg i.v. were measured by two techniques: radioreceptorassay and gas chromatography/mass spectrometry (GC/MS).

Acetyl-Fentanyl

IUPAC: N-(1-Phenethylpiperidin-4-yl)-N-phenylacetamide
Acetylfentanyl (acetyl fentanyl) is an opioid analgesic drug that is an analog of fentanyl. Studies have estimated acetylfentanyl is between five to fifteen times more potent than heroin. Additionally it is reported as being 80 times more potent than morphine, and 15 times less potent than fentanyl. It has never been licensed for medical use and has only been sold illegally as a designer drug. Acetylfentanyl was discovered at the same time as fentanyl itself and had rarely been encountered on the illicit market in the late 1980s, but was never commonly used. However in 2013, Canadian police discovered a group distributing over 3 kilograms and 12,400 pills of desmethyl fentanyl equal to 117,400 doses. As a μ-opioid receptor agonist, acetylfentanyl may serve as a direct substitute for heroin or other μ-opioid receptor agonist substances in opioid dependent individuals. Side effects include itching, nausea, and respiratory depression, which can be potentially life-threatening.

Deaths

The Centers for Disease Control and Prevention (CDC) issued a health alert to report that between March 2013 and May 2013, 14 overdose deaths related to injected acetylfentanyl had occurred among intravenous drug users (ages between 19 and 57 years) in Rhode Island. After confirming five overdoses in one county, including a fatality, Pennsylvania asked coroners and medical examiners across the state to screen for acetylfentanyl. This request led to 50 confirmed fatalities and five non-fatal overdoses statewide in 2013. Another 5 deaths were reported in Jefferson Parish, New Orleans, along with three more in North Carolina.

Legal status

Canada

It is a Schedule 1 drug. As it is an analog of fentanyl and all fentanyl analogs are Schedule 1.

United States

The drug is currently operating in a legal grey area. As an analog of fentanyl, selling acetlyfentanyl intentionally for human consumption is prosecutable by the United States Department of Justice as a DEA Schedule I controlled substance. However, as the drug itself is not classified on the DEA’s schedule list if the drug is labelled “not for human consumption” it may be legal to distribute, much like bath salts have been in the past.
The illegality of the drug has been supported by the charges against individuals for distribution of acetylfentanyl and possession with the intent to distribute acetylfentanyl. The individual was sentenced to 3 years in prison by a federal court.

Overdose

Overdoses on Acetyl Fentanyl have been reported to look exceedingly similar to those of heroin and may not be detected unless using gas chromatography. Additionally, while naloxone (Narcan) is effective in treating Acetyl Fentanyl overdose, larger than normal quantities may need to be administered in order for someone to recover from an overdose