Central analgesic activity

Still further simplification of the structural requirements for central analgesic activity came from the serendipitous observation that the simple phenyl pi peri dine, meperidine... 

Additional in vivo studies on the biological activity of proanthocyani-dins investigating a series of behavioral activities (motihty, body weight gain, body temperature, motoric coordination, anticonvulsant effects and central analgesic activities) showed no or only moderate pharmacological effects [53]. On the other hand, dietary supplementation with cocoa pro-cyanidin supplements can dose-dependently prevent the development of hyperglycemia in diabetic obese mice [54]. 

CT Dooey, NN Chung, BC Wilkes, PW Schiller, JM Bidlack, GW Pasternak, RA Houghten. An all D-amino acid opioid peptide with central analgesic activity from a combinatorial library. Science 266 2019-2022, 1994. 

It has been found empirically that central analgesics that possess some degree of activity as antagonists of the effects of morphine tend to show a reduced propensity for causing physical addiction. Again empirically, it was noted that this could often be achieved by replacement of the N-methyl group by allyl, cyclopropylmethyl, or cyclobutylmethyl additional nuclear modifications often contributed to this activity. 

A common strnctnral feature required for centrally acting analgesic activity in the opioids is the combination of an aromatic ring and a piperidine ring that maintains the stereochemistry at the chiral centre, as shown below. 

Palmitoylethanolamide, isolated from rat and quinea pig brains, was shown to exhibit antiinflammatory and analgesic activity even though it does not activate central and peripheral cannabinoid receptors. Palmitoylethanolamide binds with high potency (EC50 = 3.2 1.3 nM) to the orphan G-protein-coupled receptor GPR55, which as mentioned above, may represent a new cannabinoid receptor. 

It has been found empirically that central analgesics that possess some degree of activity as antagonists of the... 

Caffeine is a known inhibitor of phosphodiesterase. Caffeine has an effect on calcium-mediated signalling namely it causes an increase of cAMP activity. Caffeine also has a competitive effect on the central adenosine receptor and is thought to increase analgesic activity. It is also known to be somewhat effective... 

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