Antagonists prostaglandin

Procaine forms poorly soluble salts or conjugates with some drugs [12], and was reported to be a strong prostaglandin antagonist and a weak agonist [13]. It is used in the treatment of malignant hyperpyrexia [14-17]. Procaine hydrochloride was also used by intravenous injection for the relief of pain in acute pancreatitis [18-21],... 

Van Rossum JM, van den Brink (1963) Cumulative dose-response curves. Arch Int Pharmacodyn 143 240-246 Vassilev P, Radomirov R (1992) Contractile effects of prostaglandin E2 in rat rectum sensitivity to the prostaglandin antagonists diphloretin and SC 19220. Prostaglandins 44 471-484... 

A series of 2-substituted 3-dimethylamino-5,6-methylene-dioxyindenes (MDIs) were developed in our laboratories (20) as intermediates in the synthesis of potential prostaglandin antagonistic indanpropionic acids (21,22). Pharmacological evaluation of these intermediate MDIs demonstrated their calcium antagonistic properties 9). The following discussion is an... 

An area which may assume future importance is that of prostaglandin antagonists. Eakins, et reported the antagonism of the smooth... 

Fried and coworkers reported the synthesis of some 7-oxa analogs of prostanoic acid and their cyclohexane analogs. Some of these compounds were found to be prostaglandin antagonists. Compounds and 49. have also been shownto produce smooth muscle responses. 

The synthetic utihty of the above transformations stems from the fact that many monoesters obtained as a result of hydrolysis may be converted to pharmaceutically important intermediates. For example, the optically active glycerol derivative (27) is a key intermediate in the production of P-blockers. Akyl derivative (25) may be converted into (5)-paraconic acid [4694-66-0] ((5)-5-oxo-3-tetrahydrofurancarboxyhc acid) that is a starting material for the synthesis of (3R)-A-factor. The unsaturated chiral cycHc monoacetate (31) is an optically active synthon for prostaglandins, and the monoester (29) is used for the synthesis of platelet activating factor (PAF) antagonists. 

Dronabinol (tetrahydrocannabinol), the active principle from cannabis and synthetic cannabinoids, nabilone and levonantradol are effective in treating nausea and vomiting in cancer chemotherapy. The mode of action is unclear but appears to involve cannabinoid CBi receptors. Cannabinoids have been shown to reduce acetylcholine release in the cortex and hippocampus, and have been suggested to inhibit medullary activity by a cortical action. Inhibition of prostaglandin synthesis and release of endorphins may also be involved in the antiemetic effect. A review of trials of dronabinol, nabilone or levonantradol concluded that while the cannabinoids were superior to placebo or dopamine receptor antagonists in controlling emesis... 

The main problem with any study of prostaglandins (PGs) is that although brain concentrations can exceed 0.1 /rg/g, they appear to be formed on demand, rather than preformed and stored and they have very short half-lives (seconds). Also specific effective antagonists remain to be developed and PGs are widely and evenly distributed, unlike many NTs. Thus any analysis of their central effects rests heavily on either studying PG release, or their effects when applied directly (icv injection). Certainly the brain has the enzymatic ability to synthesise both prostaglandins (cycloxygenase) and leukotrienes (lypoxygenase) from arachidonic acid (AA) (see Fig. 13.8) and a number of central functions have been proposed for them (see Piomelli 1994). 

M., Humphrey, G.R. et al. on the long term factory process for the production of a prostaglandin D2 receptor antagonist - unprecedented asymmetric hydrogenation of an indole Fxo-Cyclic Trisubstituted a,(i-Unsaturated Acid. 

Marcheselli, V. L. and Bazan, N. G. Sustained induction of prostaglandin endoperoxide synthase-2 by seizures in hippocampus. Inhibition by a platelet-activating factor antagonist. / Biol. Chem. 271 24794-24799,1996. 

Sepsis involves a complex interaction of proinflammatory (e.g., tumor necrosis factor-a [TNF-a] interleukin [IL]-1, IL-6) and antiinflammatory mediators (e.g., IL-1 receptor antagonist, IL-4, and IL-10). IL-8, plateletactivating factor, and a variety of prostaglandins, leukotrienes, and thromboxanes are also important. 

---