In chemistry and pharmacology, functional analogs are chemical compounds that have similar physical, chemical, biochemical, or pharmacological properties. Functional analogs are not necessarily structural analogs with a similar chemical structure. [1] An example of pharmacological functional analogs are morphine, heroin and fentanyl, which have the same mechanism of action, but fentanyl is structurally quite different from the other two. [2]
Morphine is a pain medication of the opiate family that is found naturally in a number of plants and animals, including humans. It acts directly on the central nervous system (CNS) to decrease the feeling of pain. It can be taken for both acute pain and chronic pain and is frequently used for pain from myocardial infarction, kidney stones, and during labor. Morphine can be administered by mouth, by injection into a muscle, by injection under the skin, intravenously, injection into the space around the spinal cord, or rectally. Its maximum effect is reached after about 20 minutes when administered intravenously and 60 minutes when administered by mouth, while the duration of its effect is 3–7 hours. Long-acting formulations of morphine also exist.
Fentanyl, also spelled fentanil, is an opioid used as a pain medication and together with other medications for anesthesia. It is also used as a recreational drug, often mixed with heroin or cocaine. It has a rapid onset and its effects generally last under two hours. Medically, it is used by injection, nasal spray, skin patch, or absorbed through the cheek (transmucosal) as a lozenge or tablet.
Carfentanil or carfentanyl is a structural analog of the synthetic opioid analgesic fentanyl. Carfentanil was first synthesized in 1974 by a team of chemists at Janssen Pharmaceutica which included Paul Janssen. The effects of carfentanil, including overdose, can be reversed by naloxone. Carfentanil is legally controlled in most jurisdictions, but has veterinary uses for anaesthetising large animals, such as elephants and bears.
A designer drug is a structural or functional analog of a controlled substance that has been designed to mimic the pharmacological effects of the original drug, while avoiding classification as illegal and/or detection in standard drug tests. Designer drugs include psychoactive substances that have been designated by the European Union as new psychoactive substances (NPS) as well as analogs of performance-enhancing drugs such as designer steroids. Some of these were originally synthesized by academic or industrial researchers in an effort to discover more potent derivatives with fewer side effects and were later co-opted for recreational use. Other designer drugs were prepared for the first time in clandestine laboratories. Because the efficacy and safety of these substances have not been thoroughly evaluated in animal and human trials, the use of some of these drugs may result in unexpected side effects.
A structural analog, also known as a chemical analog or simply an analog, is a compound having a structure similar to that of another compound, but differing from it in respect to a certain component.
Nicomorphine is the 3,6-dinicotinate ester of morphine. It is a strong opioid agonist analgesic two to three times as potent as morphine with a side effect profile similar to that of dihydromorphine, morphine, and diamorphine.
Dipropanoylmorphine is an opiate derivative, the 3,6-dipropanoyl ester of morphine. It was developed in 1972 as an analgesic. It is rarely used in some countries for the relief of severe pain such as that caused by terminal cancer, as an alternative to diamorphine (heroin) and morphine. The drug was first synthesised circa or about 1875 in Great Britain along with many other esters of morphine, all of which were shelved at the time, some of which were later developed such as heroin (1898), acetylpropionylmorphine (1923), dibenzoylmorphine, and so on. The name of this drug is also given as 3,6-dipropanoylmorphine and its 6-mono-acetylated homologue is also a longer-acting heroin-like drug, as are 3,6-diformylmorphine and 6-formylmorphine.
Ohmefentanyl is an extremely potent opioid analgesic drug which selectively binds to the µ-opioid receptor.
α-Methylfentanyl is an opioid analgesic that is an analog of fentanyl.
3-Methylfentanyl is an opioid analgesic that is an analog of fentanyl. 3-Methylfentanyl is one of the most potent opioids, estimated to be between 400 and 6000 times stronger than morphine, depending on which isomer is used.
Lofentanil is one of the most potent opioid analgesics known and is an analogue of fentanyl, which was developed in 1960. It is most similar to the highly potent opioid carfentanil (4-carbomethoxyfentanyl), only slightly more potent. Lofentanil can be described as 3-methylcarfentanil, or 3-methyl-4-carbomethoxyfentanyl. While 3-methylfentanyl is considerably more potent than fentanyl itself, lofentanil is only slightly stronger than carfentanil. This suggests that substitution at both the 3 and 4 positions of the piperidine ring introduces steric hindrance which prevents μ-opioid affinity from increasing much further. As with other 3-substituted fentanyl derivatives such as ohmefentanyl, the stereoisomerism of lofentanil is very important, with some stereoisomers being much more potent than others.
Diampromide is an opioid analgesic from the ampromide family of drugs, related to other drugs such as propiram and phenampromide. It was invented in the 1960s by American Cyanamid, and can be described as a ring-opened analogue of fentanyl.
Mirfentanil is a fentanyl derivative with strong selectivity for the μ opioid receptor. At lower doses, it antagonizes the analgesic effects of alfentanil and substitutes for naloxone in morphine-treated monkeys; however, it also reverses naloxone-precipitated withdrawal in pigeons trained to discriminate morphine from naloxone.
1-Iodomorphine is a semi-synthetic narcotic analgesic formed by halogenation of the 1 position on the morphine carbon skeleton. Halogenated morphine derivatives were first synthesised in Germany, Austria/Austria-Hungary, the United Kingdom and the United States in the period 1890 to 1930. Use of this drug increased after 1945 for the below-mentioned research. It is a research chemical which is often prepared in the laboratory when it is needed.
N-Methylnorcarfentanil (R-32395) is an opioid analgesic drug related to the highly potent animal tranquilizer carfentanil, but several thousand times weaker, being only slightly stronger than morphine. It was first synthesised by a team of chemists at Janssen Pharmaceutica led by Paul Janssen, who were investigating the structure-activity relationships of the fentanyl family of drugs. They found that replacing the phenethyl group attached to the piperidine nitrogen of fentanyl with a smaller methyl group, made it so much weaker that it was inactive as an analgesic in animals. However the same change made to the more potent analogue carfentanil retained reasonable opioid receptor activity, reflecting the higher binding affinity produced by the 4-carbomethoxy group.
Acetylfentanyl is an opioid analgesic drug that is an analog of fentanyl. Studies have estimated acetylfentanyl to be fifteen times more potent than morphine. It has never been licensed for medical use and instead has only been sold as a designer drug. Acetylfentanyl was discovered at the same time as fentanyl itself and had only rarely been encountered on the illicit market in the late 1980s. However, in 2013, Canadian police seized 3 kilograms of acetylfentanyl. As a μ-opioid receptor agonist, acetylfentanyl may serve as a direct substitute for heroin or other opioids. Common side effects of fentanyl analogs are similar to those of fentanyl itself, which include itching, nausea and potentially serious respiratory depression, which can be life-threatening. Fentanyl analogs have killed hundreds of people throughout Europe and the former Soviet republics since the most recent resurgence in use began in Estonia in the early 2000s, and novel derivatives continue to appear.
Furanylfentanyl (Fu-F) is an opioid analgesic that is an analog of fentanyl and has been sold as a designer drug. It has an ED50 value of 0.02 mg/kg in mice. This makes it approximately one fifth as potent as fentanyl.
4-Fluoroisobutyrylfentanyl (also known as 4-FIBF and p-FIBF) is an opioid analgesic that is an analog of butyrfentanyl and structural isomer of 4-Fluorobutyrfentanyl and has been sold online as a designer drug. It is closely related to 4-fluorofentanyl, which has an EC50 value of 4.2 nM for the human μ-opioid receptor. 4-fluoroisobutyrylfentanyl is a highly selective μ-opioid receptor agonist whose analgesic potency is almost ten times of that reported for morphine.
Diphenpipenol 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 related to compounds such as MT-45 and AD-1211, but diphenpipenol is the most potent compound in the series, with the more active (S) enantiomer being around 105 times the potency of morphine in animal studies. This makes it a similar strength to fentanyl and its analogues, and consequently diphenpipenol can be expected to pose a significant risk of producing life-threatening respiratory depression, as well as other typical opioid side effects such as sedation, itching, nausea and vomiting.
 | This pharmacology-related article is a stub. You can help Wikipedia by expanding it. |