Analgesic drug development

Elliott K, Kest B, Man A, Kao B, Inturrisi CE. (1995). N-methyl-D-aspartate (NMDA) receptors, mu and kappa opioid tolerance, and perspectives on new analgesic drug development. Neuropsychopharmacology. 13(4) 347-56. 

Woolf CJ, Max MB. Mechanism-based pain diagnosis issues for analgesic drug development. Anesthesiology 2001 95(l) 241-249. 

The development of the first effective analgesic drug, opium, was almost certainly adventitious, and occurred in prehistoric times. The use of the dried exudate from slitting the immature capsule of the opium poppy, Papaver somniferum, as an analgesic, sedative and euphoriant, has a long folkloric history. Isolation of the principal active component morphine (1) as a pure crystalline compound represented one of the early landmarks in organic chemistry. 

Metopon (methyldihydromorphinone) manifests the properties of tolerance and liability to addiction, but it is about twice as effective as an analgesic, and its duration of action is equal to that of morphine. Tolerance to metopon and physical dependence on the drug develop more slowly than in the case of morphine. In therapeutic doses, it produces little or no respiratory depression and still less mental dullness. Metopon thus possesses many advantages over morphine but is no longer available commercially. 

Tetrahydropalmatine has strong analgesic, sedative, and hypnotic effects 544, 553-563). They are produced by the (—) type hut not by the (+) type. In rabbits the analgesic effect was weaker than that of morphine, but the tolerance for this drug developed at a far slower rate practically without any side effects. In experiments on patients tetrahydropalmatine had a weaker analgesic effect but a stronger hypnotic effect than morphine. Application of doses of 10 mg/kg of tetrahydropalmatine to white mice led to disappearance of the conditioned reflexes whereas the unconditioned reflexes were maintained. For the influence of (+ )-tetrahydropalmatine and other alkaloids on gastric ulcers in experimental animals, see Soji et al. (564). Variously substituted tetrahydroberberine and tetrahydropseudoberberine derivatives act as tranquilizers (565-569). 

During the last years fast dispersible tablets for the disintegration in the mouth were developed and commercialized e.g. Flash tabs . First of all this applies to analgesic drugs. For this kind of tablets the superdisintegrants like crospovidone are used to obtain a disintegration within less than one minute. A typical example is ibuprofen [654,655]. 

The development of narcotic analgesics is a good example of the traditional approach to medicinal chemistry and provides good examples of the various strategies which can be employed in drug development. We can identify several stages ... 

The catalytic hydrogenation of nitrobenzene to p-amionophenol (PAP) under phase-transfer conditions is an industrially important process that was first reported in 1940 (1). PAP is an important intermediate which has been used in the production of analgesic drugs, (2) photographic developers and dyes (3). The... 

PLANT COMPOUNDS THAT HAVE CONTRIBUTED TO THE DEVELOPMENT OF ANALGESIC DRUGS... 

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