Antinociceptive agent

In the context of preparing analogues of chiral l,2-dimethyl-3-(2-naphthyl)-3-hy-droxy-pyrrolidines, which are known non-peptide antinociceptive agents, Collina and coworkers have reported the solvent-free dehydration of hydroxypyrrolidines to pyrrolines under microwave conditions (Scheme 6.141) [278]. In a typical experiment, the substrate was adsorbed onto a large excess of anhydrous ferric(III) chloride on silica gel and then irradiated as a powder under microwave conditions for 30 min at 150 °C. The microwave method leads to dehydration without racemiza-tion and provides higher yields in considerably shorter times than the conventionally heated process. 

Drugs that modify the activity of the kallikrein-kinin system are available, though none are in wide clinical use. Considerable effort has been directed toward developing kinin receptor antagonists, since such drugs have considerable therapeutic potential as anti-inflammatory and antinociceptive agents. Competitive antagonists of both and B2 receptors are available for research use. Examples of B receptor... 

Raffa, R. B. and Martinez, R. P. The glibenclamide-shift of centrally-acting antinociceptive agents in mice, Brain Research 1995, 677, 277-282. 

Seguin, L., Le Marouille-Girardon, S., Millan, M.J. Antinociceptive profiles of non-peptidergic neurokinini and neurokinin2 receptor antagonists a comparison to other classes of antinociceptive agent,... 

Compound (-) 77 is a good antinociceptive agent (3 x morphine MHP sc and 2 x (—)-N-methylmorphinan), and it seems, therefore, that the 6-oxo function plays some part in events at opioid receptors. 

Rather more distant morphinan relatives are compounds of the general structure 149 (n = 1 or 2) prepared as bridged arylmorphans.(l41,142) They were, at best, weak antinociceptive agents. 

Giovannoni MP, Vergelli C, Ghelardini C, Galeotti N, Bartolini A, Kal Piaz V (2003) (3-Chlorophenyl)piperazinylpropyl]pyridazinones and analogues as potent antinociceptive agents. J Med Chem 46 1055-1059... 

Compound (156) was reported (193) to be a potent antinociceptive agent, but there was little difference between an analgesic dose and one producing salivation. Analogs of (156) were prepared (194) in attempts to separate... 

Kappa Receptors. Like jx and 6 receptors, activation of k opioid receptors can produce antinociceptive effects. However, the effectiveness of k opioid agonists as antinociceptive agents varies in different types of pain (see Ref 146), and k agonists are less effective in thermal antinociceptive assays involving more intense stimuli. 

A variety of benzomorphans have been prepared with various combinations of alkyl substituents (methyl, ethyl, propyl) at the 5 and 9 positions (seeRefs. 283,388). The alkyl group at the 9 positioncan be oriented either a, in which the substituents in the 5 and 9 positions are cis, or /3, in which these substituents are trans (see 92, Fig. 7.21). The synthetically minor /3 isomers, which have the opposite stereochemistry from that of the corresponding position in morphine (C,), are more potent than the a isomers as antinociceptive agents (see Refs. 283, 388). Attachment of a 3-alkanone side chain at the 9/3 position of metazocine (94) yielded a series of potent compounds... 

Kumar V, Alexander MD, Bell MR, Eissenstat MA, Casiano FM, Chippari SM, Haycock DA, Lutinger DA, Kuster JE, Miller MS, Stevenson J1, Ward SJ( 1995) Morpholinoalkylin denes as antinociceptive agents novel cannabinoid receptor agonists. Bioorg Med Chem Lett 5 381-386... 

Another cj-conotoxin CVID isolated from Conus catus has been shown to have similar potency as u>-conotoxin MVIIA but lower levels of toxicity at comparable therapeutic levels/ ° and has been shown to have potential as an antinociceptive agent. The highly selective Ci -conotoxin GVIA, isolated from... 

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