Cyclooxygenase (COX) is the enzyme catalysing oxidation of arachidonic acid to hydroperoxy endoperoxide (PGG2) and its subsequent reduction to hydroxy endoperoxide (PGH2). It is thus an important therapeutic target for the modulation of the prostaglandin pathway. Recent studies have demonstrated the existence of a second isoform of COX. Both the isoforms have a molecular weight of 71K with 63% amino acid homology. The human COX-2 gene is however a 8.3Kb small immediate early gene and is induced by most of the stimuli associated with inflammation. COX-2 has thus been implicated in pathological roles of COX while constitutive COX-1 is said to be involved in physiological functions. Indeed, COX-2 has now been associated with inflammation, hyperalgesia, angiogenesis, neuromodulation, cancer and Alzheimer's disease, giving rise to the opportunity of modulating these conditions with selective inhibitors of COX-2. The recent X-ray structural analysis for COX-2 has paved the way for development of a whole new range of agents with selectivity for this isoform, thereby sparing the physiological functions. Here in this review, an attempt has been made to elucidate the role of COX-2 in these conditions and to evaluate the various COX-2 inhibitors that are in different stages of development or are presently available. From the present knowledge of COX-1 and COX-2 an effort has been made to reclassify NSAIDs based on the selectivity in inhibiting the isoforms.

Motilin is a naturally occurring gastrointestinal (GI) polypeptide which stimulates GI smooth muscle contractility through motilin receptors. Motilides are members of macrolide family which exhibit prokinetic activity by acting as motilin receptor agonists but lack antibacterial activity. The mechanism for smooth muscle contractile effect of motilin/motilides involve activation of voltage sensitive Ca2+ channels and release of Ca2+ from intracellular Ca2+ stores via G protein linked phospholipase C/inositol 1,4,5 trisphosphate pathway. None of the currently available drugs qualify as an ideal prokinetic agent due to variable efficacy and side effects. Motilides possess potent gastroprokinetic activity and do not produce side effects. They may be considered as drugs of choice for the treatment of various GI functional motor disorders like gastro-oesophageal reflux disease, gastroparesis, postoperative ileus, scleroderma and idiopathic pseudo-obstruction.

Objectives: To investigate whether tamoxifen, oestradiol and 4-monohydroxytamoxifen inhibit entry of calcium into rat myometrium. Methods: Pieces of myometrium were incubated in media containing tamoxifen, oestradiol or 4- monohydroxytamoxifen, in the presence or absence of known myometrial spasmogens (80 mM KCl or 1.28 nM oxytocin). Following incubation the tissues were dried and the uptake of 45 Ca 2+ measured. Results: OH-tamoxifen inhibited the entry of 45 Ca 2+ entry in both normal (5.9 mM KCl) and high potassium (80 mM KCl) media while tamoxifen and oestradiol inhibited 45 Ca 2+ entry only in high potassium media. 20 (M 17(-oestradiol also inhibited calcium influx in oxytocin (1.28 nM) stimulated tissues, no inhibition was observed with tamoxifen. Conclusions: Tamoxifen and its metabolite, 4-monohydroxytamoxifen (OH-tamoxifen) may obstruct ion-channel, but not receptor, mediated entry of calcium into rat myometrium.

Objectives: To study the inhibitory effect of pinacidil and cromakalim on the contractile response induced by electrical field stimulation (EFS) in atropinized rat urinary bladder strip. Methods: The rat urinary bladder strips were stimulated by two parallel platinum wire electrodes. Electrical impulses for field stimulation of intrinsic nerves were delivered for 1ms duration at 60v and frequency ranging from 0.5-64 Hz. The control contractile response to EFS was evoked by the application of 5sec trains of impulses at a constant frequency. The effect of pinacidil and cromakalim on the contractile responses induced by EFS on atropinized tissues was evaluated. Results: The mean EF50 value of frequency related contractile response curve was ranging from 3.45- 3.92 Hz. In presence of pinacidil and cromakalim the EF50 values were significantly higher than that of their corresponding control EF50 values. In presence of atropine, pinacidil and cromakalim further increased the EF 50 values. Conclusion: K+ - channel openers in atropinized rat urinary bladder smooth muscle potentiate the inhibitory effect of atropine on contractile response induced by EFS.

Objective: To study the anticonvulsant effect of fluoxetine against electrically induced seizures. Methods: The anticonvulsant effect of fluoxetine in different doses following both acute and chronic administrations, was assessed in a modified version of increasing-current electroshock seizure test in mice. The increase in current required to induce the tonic hindlimb extension (seizure threshold current) was observed as a parameter of anticonvulsant effect. Results: Fluoxetine produced significant anticonvulsant effects in some of the doses studied. Significant increase in seizure threshold current was observed after 7, 14 and 21 days of treatment. Conclusion: Fluoxetine exhibited anticonvulsant activity against ICES induced seizures.

Objective: To investigate whether nicotinic acid, gemfibrozil and clofibrate exert their hypolipidemic effect by changing the activity of hepatic phosphatide phosphohydrolase (PAP). Methods: Male Wistar rats were intraperitoneally treated with one of the following: nicotinic acid, clofibrate, gemfibrozil, corresponding vehicle. All animals were given corn oil ( p.o.) 2 h before injection. They were sacrificed at different time intervals and PAP enzyme activity was measured in liver homogenate. Serum triacylglycerol and cholesterol levels were also estimated. Results: Nicotinic acid inhibited PAP activity 35% with simultaneous decrease in serum triacylglycerol (29%) and cholesterol (22%) concentrations. Clofibrate also inhibited PAP activity (31%) with parallel decline in the concentrations of triacylglycerol (26%) and cholesterol (19%). Similar patterns were observed in rats injected with gemfibrozil in which the fall in PAP activity, triacylglycerol and cholesterol concentrations were 17%, 43% and 12% respectively. Conclusion: Hypolipemic effects of these compounds are, at least in part, resulted from inhibition of hepatic PAP activity, a key enzyme in the lipid metabolism.

Objective : To evaluate the analgesic and antiinflammatory activities of hydroalcoholic extract of Vitex negundo leaves and to elucidate possible mechanism(s) of its pharmacological activities. Methods : The analgesic activity of Vitex negundo leaf extract (VLE) [500 and 1000 mg/kg] was studied using acetic acid induced writhing test in mice for assessing peripheral analgesic effect and tail immersion test in mice for assessing central analgesic effect. The antiinflammatory activity of VLE (500 and 1000 mg/kg) was studied by using the models of carrageenin-induced rat paw oedema and carrageenin-induced granuloma pouch in rats for assessing the effect on acute and subacute inflammations, respectively. Isolated rat uterus was used to study the involvement of prostaglandins in the analgesic and antiinflammatory activities of VLE. The chemical analysis of the VLE was done using HPTLC technique. Results : VLE significantly increased the reaction time and decreased the writhing movements in mice in acetic acid-induced writhing test. There was a significant increase in the reaction time in tail immersion test. VLE significantly decreased the rat paw oedema volume at higher dose. It also significantly decreased the formation of granuloma pouch in rats. VLE had inhibitory action on oxytocin-induced contractions in isolated horns of uterus primed with oestradiol. Bioflavonoids were found to be present in VLE. Conclusion : VLE may have both central and peripheral analgesic action. VLE also possesses antiinflammatory activity which was more pronounced on subacute rather than on acute inflammation. The analgesic and anti- inflammatory action of VLE can be attributed to its flavonoid contents, which are known to act through inhibition of prostaglandin biosynthesis.

Objectives: To study about the rationality of the different fixed dose drug combinations (FDC) prescribed by doctors. Methods: A retrospective study was conducted after collecting prescription from patients attending private clinics and Government hospitals. The rationality of FDC formulations was studied on the basis of FDCs recommended by WHO in its list of essential drugs. Results: Audit of the prescriptions reveals that 75% of the prescriptions contained FDC formulations. However, FDCs in accordance with recommended WHO list of FDCs were only 11%. The most commonly prescribed were antimicrobials and analgesics which constitute nearly 31% of the total FDCs prescribed. In 52% of the prescriptions, the prescribed FDCs contained ingredients which were not essential for the desired therapeutic effect. Conclusion: 80% of the FDCs prescribed did not conform to the recommended WHO list. However, the use of certain FDCs were highly justified and rational.

Objectives: To study the effect of some serotonerigc agents on lithium-pilocarine model of status epilepticus in rats. Methods: Pilocarpine (30 mg/kg, s.c.) was given 24 hrs after administration of lithium sulphate (3 meq/ kg, i.p.) to induce seizures. The test drugs were given 45 minutes prior to administration of pilocarpine, except pCPA which was given 72 hrs before lithium. The effect on severity of convulsions was observed. Results: Dexfenfluramine and cisapride significantly potentiated the seizure, whereas buspirone, mianserine, cyproheptadine, fluoxetine, ondanstron and pCPA significantly protected animals from the lithium pilocarpine induced seizures. Conclusion: Thus the study suggests that the blockade of postsynaptic 5-HT receptors and inhibition of serotonergic transmission inhibit lithium-pilocarpine-induced seizure.

Objective: To study the effect of fresh juice (FJ) and ethyl acetate extract (EE) of Clerodendron colebrookianum (CC) leaves on glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) in the blood and liver of male Sprague Dawley rats. Methods: Three groups of rats each comprising of 10 animals were selected for this experiment. Group I served as control and the other two groups were orally administered with FJ and EE extracts respectively, upto a period of 28 days. The GOT and GPT were estimated on days 7, 14, 21 and 28 using an autoanalyser. Result: FJ treatment significantly reduced the SGOT level only. After EE administration SGPT was increased more than 9-10 fold over the respective control, while the SGPT declined significantly on days 7 and 14 of experimentation. Sustained elevation in the level of liver GPT was recorded in the EE treated animals while the liver GOT was found to be increased on days 7 and 14 but returned to control level on day 28. Conclusion: FJ and EE of CC leaves affect the transaminases levels, but no liver cell damage occurred in rats.