Analgesics and anti-inflammatory agents

There are only two mechanistic classes of pain-relieving drugs. The opiate alkaloids and several groups of synthetic compounds act by mimicry of 

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Due to the large number of references which appeared to be worth mentioning, it became necessary to divide this review into two parts. The present part deals mainly with pyridazines as chemotherapeutics, antithrombotics, antise-cretory and anti-ulcer agents, analgesic and anti-inflammatory agents as well as with various central nervous system stimulants and depressants. Part 2 of this review, which is planned for a future volume of this Series, will be devoted mainly to compounds which act on the cardiovascular system and to a discussion of miscellaneous additional pharmacological activities of pyridazine derivatives. 

In contrast to drugs from natural sources, those drugs that are made entirely in the laboratory are either achiral or, if cliiial, are often produced and sold as racemic mixtures. Ibuprofen, for example, has one chirality center and is sold commercially under such trade names as Advil, Nuprin, and Motrin as a racemic mixture of R and 5. It turns out, however, that only the 5 enantiomer is active as an analgesic and anti-inflammatory agent. The R enantiomer of ibuprofen is inactive, although it is slowly converted in the body to the active S form. 

Allopathic drugs Analgesic and anti-inflammatory agents (for example aminophenazone, indometacin, phenylbutazone), benzodiazepines, glucocorticoids, sulfonylureas, thiazide diuretics, thyroid hormones... 

Ketoprofen has been shown to be a potent analgesic with effects equivalent to pentazocine and meperidine (pethidine) in the treatment of postoperative pain in humans (Avouac Teule 1988). In horses, ketoprofen has also been shown to be an effective analgesic and anti-inflammatory agent. In one study, the pharmacodynamics of ketoprofen (2.2 mg/kg) were studied in a non-immune acute inflammatory model (Landoni Lees 1995a). In this study, ketoprofen inhibited... 

Forrester S D, Troy G C 1999 Renal effects of nonsteroidal anti-inflammatory drugs. Compendium on Continuing Education for the Practicing Veterinarian 21 910-919 Fry S W, Seeff L B 1995 Hepatotoxicity of analgesics and anti-inflammatory agents. Gastroenterology Clinics of North America 24 875-905... 

Chapter 8 Delta l-THC-7-oic acid Analgesic and Anti-inflammatory Agents Metabolites of Al-Thtrahydrocannabinol... 

This invention is based on the discovery that Al-THC-7-oic-acid is a potent analgesic and anti-inflammatory agent, and that when administered directly into the stomach is non-ulcerogenic. As a result, this non-psychoactive metabolite of THC can be used as a therapeutic agent for such purposes as the treatment of chronic pain and tissue inflammation often associated with illnesses such as rheumatoid arthritis. 

It has now been discovered that this metabolite, when administered to laboratory animals in a standard pharmacological assay for analgesia (see exemplification), produces a pain-relieving effect which is merely equivalent to that of naproxen (6-Methoxy-a-methyl-2-naphthaleneacetic acid), a popular analgesic and anti-inflammatory agent in use today. Thus, the therapeutic effects of the Al-THC-7-oic-acid metabolite can be separated from the psychoactive effects of THC, the parent substance. 

The present invention is generally directed to non-psychoactive derivatives of A6-THC-7-oic acid, which have been shown to be potent analgesic and anti-inflammatory agents and to possess leukocyte antiadhesion activities. The invention is further related to the use of these derivatives as therapeutic agents in the treatment of pain and tissue inflammation, especially that associated with long-term illnesses such as rheumatoid arthritis. 

Brady, L.S. Lynn, A.B. Glowa, J.R. Le D. Herkenham, M. . Repeated Electroconvulsive Shock Produces Long-lasting Increases in Messenger RNA Expression of Corticotropin-releasing hormone and Tyrosine Hydroxylase in Rat brain. Therapeutic implications. J Clin Invest 1994 94 1263-1268. Burstein, S. Delta l-THC-7-oic acid and Analgesic and Anti-inflammatory Agents 1989 US 4,847,290... 

Acetylsalicylic add is widely used as an analgesic and anti-inflammatory agent. In the body it is hydrolyzed to salicylate. The assay of salicylate by enzyme electrodes is based on the reaction of salicylate hydroxylase (EC 1.14.13.1) ... 

A key step in a synthesis of ketorolac, an analgesic and anti-inflammatory agent, involves an intramolecular nucleophilic displacement of a methanesulfonyl group activated by a 5-ketone. ... 

The asymmetric dihydroxylation has been applied in many synthetic sequences and is discussed further in Part B, Chapter 12. For example the dihydroxylation was the starting point for enantioselective synthesis of 5-ibuprofen and a similar route was used to prepare -naproxen, which contains a methoxynaphthalene ring. Ibuprofen and naproxen are examples of the NSAID class of analgesic and anti-inflammatory agents. 

Ketorolac, an analgesic and anti-inflammatory agent, is equal to morphine sulfate on a weight-to-weight basis for the alleviation of post-operative pain. Atorvastatin lowers chlolesterol levels. 

Applying the strategy of direct coupling of pyrroles with carbonyl compounds, Baran et al. developed a short enantioselective synthesis of (5)-ketorolac, Syntex s analgesic and anti-inflammatory agent.The antipode of ketorolac is more potent and causes fewer side effects. 

A series of benzothiophene carboxamides, available from previous studies (IIIUBIIOI) were evaluated as analgesics and anti-inflammatory agents. Of these, N-benzyl-3-bromo-, 3-bromo-N-(4-fluorobenzyl)- and 3-bromo-N-(2-phenylethyl)-benzo[ ]thiophene-2-carboxamides attenuate nocipception and inflammation at lower concentrations than classical NSAIDs such as ibuprofen. These compounds are well tolerated and metabolized to avoid any toxicity... 

The recognition and control of nociceptor transduction and development of primary hyperalgesia are key to reducing the intensity and duration of acute pain. Nociceptor sensitization leads to reductions in noxious thresholds, increased pain disability, and delayed rehabilitation. The physiological response to transduction and the initiation of nociception can be limited or eliminated by peri operative administration of non-opioid analgesics and anti-inflammatory agents (e.g. NS AIDS, steroids). Although opioids can inhibit... 

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