| 1. |
- Fowler, Christopher J, et al.
(författare)
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The case for the development of novel analgesic agents targeting both fatty acid amide hydrolase and either cyclooxygenase or TRPV1
- 2009
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Ingår i: British Journal of Pharmacology. - : John Wiley & Sons. - 0007-1188 .- 1476-5381. ; 156:3, s. 412-419
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Tidskriftsartikel (refereegranskat)abstract
- Although the dominant approach to drug development is the design of compounds selective for a given target, compounds targeting more than one biological process may have superior efficacy, or alternatively a better safety profile than standard selective compounds. Here, this possibility has been explored with respect to the endocannabinoid system and pain. Compounds inhibiting the enzyme fatty acid amide hydrolase (FAAH), by increasing local endocannabinoid tone, produce potentially useful effects in models of inflammatory and possibly neuropathic pain. Local increases in levels of the endocannabinoid anandamide potentiate the actions of cyclooxygenase inhibitors, raising the possibility that compounds inhibiting both FAAH and cyclooxygenase can be as effective as non-steroidal anti-inflammatory drugs but with a reduced cyclooxygenase inhibitory 'load'. An ibuprofen analogue active in models of visceral pain and with FAAH and cyclooxygenase inhibitory properties has been identified. Another approach, built in to the experimental analgesic compound N-arachidonoylserotonin, is the combination of FAAH inhibitory and transient receptor potential vanilloid type 1 antagonist properties. Although finding the right balance of actions upon the two targets is a key to success, it is hoped that dual-action compounds of the types illustrated in this review will prove to be useful analgesic drugs.
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| 3. |
- Naidu, P. D., et al.
(författare)
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Seasonal sea surface temperature contrast between the Holocene and last glacial period in the western Arabian Sea (Ocean Drilling Project Site 723A): Modulated by monsoon upwelling
- 2005
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Ingår i: Paleoceanography. - 0883-8305. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Annual, summer, and winter sea surface temperatures (SSTs) in the western Arabian Sea were reconstructed through the last 22 kyr using artificial neural networks (ANNs) based on quantitative analyses of planktic foraminifera. Down-core SST estimates reveal that annual, summer, and winter SSTs were 2, 1.2, and 2.6degreesC cooler, respectively, during the last glacial period than in the Holocene. A 2.5degreesC SST increase during Termination 1A (hereinafter referred as glacial to Holocene transition) in the western Arabian Sea. The study reveals a strong seasonal SST contrast between winter and summer from 18 to 14 calendar kyr owing to the combined effect of weak upwelling and strong cold northeasterly winds. Minor or no seasonal SST changes were noticed within the Holocene period, which is attributed to the intense upwelling during the summer monsoon. This causes a lowering of SST to values similar to those of the winter season in analogy with the present day. A 3degreesC rise in winter SSTs during the glacial to Holocene transition coincides with a strengthening of the monsoon, suggesting a link between winter SST and monsoon initiation from the beginning of the Holocene. Strikingly, annual, summer, and winter SSTs show a cooling trend from similar to8 ka to the present day, implying tropical cooling in the late Holocene.
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