Analgesics, synthetic

Considerable progress has also been made with the alternative line of work, the search for a synthetic analgesic as effective as morphine and without its disadvantages. The work of the American Committee has shown that it is possible to produce analgesics with a dibenzofuran or carbazole nucleus in place of the phenanthrene or phcnanthrylene oxide nucleus of morphine and it is stated that synthetic products with analgesic potency equal to that of codeine have been prepared. In the 1938 report moderate analgesic potency was recorded for preparation No. 421, 9-methyl-2-(l-hydroxy-3-diethylamino)-propylcarbazole at 10 mgm. by injection. 

A useful review of information on pethidine has been published by Batterman and Himmelsbach, and an admirable summary of information on synthetic analgesics has been provided by Morrison and Rinderknecht. °( >... 

Eddy, N.B. and Leimbach, D., Synthetic analgesics II-Dithienylbutenyl and dithienylbuty-lamines, /. Pharmacol. Exp. Ther., 107, 385-393, 1953. 

Beckett, A.H., Casey, A.F. Synthetic analgesics stereochemical considerations./. Pharm. Pharmacol, 1954, 6, 986-999. 

J. Helleibach, O. Schnider, H. Besendorf and B. Pellmont, Synthetic Analgesics,... 

N. B. Eddy and E. L. May, Synthetic Analgesics, Part IIB, 6,1-Benzomorphans, Pergamon, Oxford, 1966... 

Ehrhard and Schauman produce synthetic analgesics (meperidine, methadone)... 

It is centrally acting synthetic analgesic compound that is not derived from natural sources nor is chemically related to opiates. It acts via opioid receptors in CNS to produce analgesia and has no abuse potential. It also inhibits the reuptake of noradrenaline and serotonin. 

Meperidine (Schedule II) is a synthetic analgesic with opiate activity. It has 10-20% of the potency of morphine with all of the addictive side effects. It has a rapid onset of action and duration which makes its useful for relieving the pain associated with labor or as a preanesthetic before surgery. Its biotransformation produces normeperidine which has been associated with seizures. It was a botched clandestine attempt to synthesize a meperidine modification which produced the toxic drug that induced parkinson-type destruction of DA neurons in its users. 

During the late 1930s some 4-phenylpiperidine derivatives were examined as potential spasmolytics on the basis of their chemical relationship to atropine. The antinociceptive properties of one member, ethyl 1-methyl-4-phenyl-piperidine-4-carboxylate, was detected in screening tests and the compound was subsequently introduced into clinical use by Eisleb and Schaumann in 1939. The compound, well known as pethidine in Europe and meperidine in North America (proprietary names include Demerol, Dolantin, and Dolosal), was soon in widespread use for the relief of pain, and it is remarkable how pethidine, the original non-opioid-derived opioid analgesic, has retained its popularity for many years in the face of competition from other synthetic analgesics introduced since 1939. 

Pethidine, introduced in 1939, was the first fully synthetic analgesic with morphine-like activity. 

Fraser, H. and Isbell, H., Human pharmacology and addictiveness of certain dextroisomers of synthetic analgesics, B. Narcotics, 14, 25, 1962. 

Narcotics are divided into naturally occurring, semisynthetic, and synthetic derivatives. The naturally occurring analgesics consist of morphine and codeine (methylmorphine). The semisynthetic analgesics include hydromorphone (Dilaudid) and hydrocodone (Dicodid). The synthetic analgesics consist of meperidine (Demerol), alphaprodine (Nisentil), methadone (Dolophine), propoxyphene (Darvon), and pentazocine (Talwin). 

D Amour FE, Smith DL (1941) A method for determining loss of pain sensation. J Pharm Exp Ther 72 74-79 Eddy NB, Leimbach D (1953) Synthetic analgesics. II. Dithienylbutenyl- and dithienylbutymamines. J Pharm Exp Ther 107 385-393... 

P A J Janssen, Synthetic Analgesics Parti Diphenylpropylamines, Pergamon Press, New York (1960)... 

Isolation of pure plant principles (e.g.. alkaloids) from the natural sources and their irlcntirication with analgesic action. t. Development of organic chemistry and the first synthetic analgesics... 

Grewe, in 1946, approached the problem of synthetic analgesics from another direction when he synthesized the tetracyclic compound that he ftrst named morphan and then revised to A(-mcthylmorphinan. The relationship of thiseom-pound to morphine is obvious. 

Janssen. P A J.. Synthetic Analgesics Part I Diplienylpiopyhiminev New York. Perganion Press. PJftO. 

Another example of assay testing involves diclofenac sodium, which is a synthetic analgesic and an anti-inflammatory drug available as delayed release tablets (Fig. 8). ... 

MPPP, also referred to as meperidine, is a synthetic analgesic with morphinelike properties. If the chemical reaction used to synthesize MPPP is not carefully regulated, a toxic by-product is also produced. When this latter molecule, MPTP, is inadvertently consumed, it is converted in the brain to MPP+, a neurotoxic agent, in an oxidation reaction catalyzed by monoamine oxidase (see p. 517). 

C- and N-Substituted mono- and bicyclic piperidines as new synthetic analgesics and anesthetics 01MI96. 

In addition to modifications of the morphine molecule, many purely synthetic analgesics have been produced, the first of these, pethidine (meperidine), having been synthesized in 1939 in an attempt to make a substitute for atropine (276). As in the case of heroin, pethidine was at first thought to be nonaddictive. It has been followed by a hundred or so other compounds of several different types, but, as with the morphine derivatives, none, with the possible exception of pentazocine, has been found to have analgesic without addictive properties. However, it seems that the two effects may not be entirely inseparable, as diphenoxylate, which has come into use as an antidiarrheal drug, has been found to possess the power to cause addiction but no analgesic action at all (277). 

Some remarks on the development of synthetic analgesics with morphine-like effect... 

Another summary with special reference to the chemical structure of opium derivatives and allied synthetic substances and their pharmacodynamic action is supplement No. 138 to the Public Health Reports of the U.S. Public Health Service entitled Studies on Drug Addiction and pubUshed in 1938 (2). Synthetic analgesics have been considered subsequently in many review s. Extensively consulted in the preparation of this article were the reviews by Fellows and Ullyot (3), Lee (4), Wikler (5), Isbell and Fraser (6), Beckett (7), Schaumann (8), and Schoen (9). This review will mainly be concerned with analgesia, addiction, and fate, of morphine and related analgesics. 

MethyImorphinan-3-ol] A potent synthetic analgesic related to morphine... 

---