Nitric oxide (NO) in the last decade has witnessed rapid metamorphism from being a dreaded environmental pollutant to a fundamental physiological mediator and effector. The biological activity of endothelium derived relaxing factor was attributed to NO and this led to the understanding of various physiological processes in which NO is implicated. NO is synthesized endogenously by the enzymes Nitric Oxide Synthase (NOS) in specialized tissues from its precursor L-arginine. It is released by constitutive and inducible modes and elicits its action as a neurotransmitter, physiological regulator and in host defence. NO mediates an active state of vasodilation, memory, neuroprotection, peristalsis, penile erection, immune defence and various endocrine & exocrine secretions. However excess of NO production can lead to endothelial dysfunction, platelet aggregation, atherosclerosis, reperfusion injury, septic shock, glomerular nephritis, neurodegeneration and mutagenesis. In disease conditions associated with hypoactive L-arginine/NO system and hyperactive L-arginine/NO system, NO donors and NOS inhibitors have significant therapeutic potential respectively. The future lies in the design of NO donors that lack the propensity to tolerance development and do not need cellular metabolic pathways for the release of NO. Also development of selective inhibitors of NOS would facilitate treatment in case of hyperactive L-arginine/NO pathway. This review describes the recent conceptual aspects of this new therapeutic entity and its clinical relevance.

Male erectile dysfunction (MED) is a common sexual disorder influenced by psychological, organic, physical, endocrine and neurovascular factors. Parasympathetic stimulation activates cholinergic receptors resulting in increased production of nitric oxide and vasoactive peptides which increase the cyclic guanosine monophosphate (cGMP) and thereby increasing vascular smooth muscle relaxation and vasodilation of corpus cavernosum.This causes rigid penile erection sufficient for sexual intercourse. However, in erectile dysfunction, there is an inability to achieve or maintain a penile erection. One of the current approaches in therapies for MED includes elevating levels of cGMP using phosphodiesterase (PDE) inhibitors. Sitdenafil is the first orally active, potent and competitive inhibitor of type-5 cGMP specific PDE enzyme that has been recently approved for the treatment of MED. Sildenafil is a synthetic methylpiperazine derivative that selectively inhibits PDE in human corpus cavernosum. Sildenafil has demonstrated its effectiveness in erectile dysfunction in several preclinical and clinical studies. It is well-tolerated (50-100 mg/day, p.o.) and safe agent for erectile dysfunction in patients with diabetes, traumatic spinal cord injury, psychological causes and physiological disorders. Adverse events reported include transient headache, dyspepsia, flushing, diarrhea and visual disturbance. The discovery of sildenafil has not only resulted in a huge market for drugs, but also unfolded the pathophysiology of erectile dysfunction. However, more controlled clinical studies are needed to establish the safety of sildenafil in patients with different age groups.

0bjective:To evaluate the antiulcer activity of cromakalim, a potassium channel opener, using various experimentally induced acute and chronic gastric ulcer models and to elucidate possible mechanism(s) of its antiulcer activity. Methods:The antiulcer activity of cromakalim (200 'g/kg, p.o.) was studied using experimentally induced acute gastric ulcer models such as aspirin plus pylorus-ligation, ethanol-induced acute gastric ulcers in rats and acetic acid-induced chronic gastric ulcerations in rats. In all the models studied, the antiulcer activity of cromakalim was compared with that of cimetidine (50 mg/kg, p.o.), an H2 receptor antagonist, In the aspirin plus pylorus-ligation model, the parameters studied were the ulcer index. the volume of gastric content, total acidity, total acid output, pepsin activity, total carbohydrate content (sum of total hexoses, hexosamine, fucose and sialic acid), total protein content and mucin activity. In ethanol-induced gastric ulcer model, the parameter studied was the ulcer index. In the acetic acid-induced chronic gastric ulcer model, the parameters studied were the ulcer index, total lesion area and score for intensity of gastric lesions. Results: In the aspirin plus pylorus-ligation model, cromakalim pretreatment caused a significant reduction in the ulcer index when compared with the control (aspirin plus pylorus-ligated) group. It has shown a significant reduction in the acid secretory parameters i.e. total acidity and pepsin activity whereas an increase in the volume of gastric content in the cromakalim-treated group led to an insignificant increase in total acid output when compared with the control group. Moreover, cromaklim did show an insignificant rise in mucin activity (total carbohydrates to protein ratio). In all the parameters, cimetidine showed a significant protective effect against ulcerations. Both cromakalim and cimetidine showed a significant reduction in the ulcer index against ethanol-induced gastric ulcerations in rats showing their cytoprotective activity. In the acetic acid-induced chronic gastric ulcer model, cromakalim showed a significant reduction in the ulcer index, total lesion area and score for intensity of gastric ulcerations and these results were comparable with those of cimetidine. Conclusion: Cromakalim possesses antiulcer activity against both acute and chronic gastric ulcer models and these results were comparable with those of cimetidine. The antiulcer activity of cromakalim can be attributed to its cytoprotective action and inhibition of the acid secretory parameters.

0bjective:To study the gastric secretory changes induced by antiulcer property of captopril and the role of prostaglandins in them. Methods: The effect of single dose of captopril and famotidine on different gastric parameters like ulcer index, pH. total acidity, mucopolysaccharide content and surface tension of gastric juice was studied by pyloric ligation alone and after pretreatment with ibuprofen. Results: Captopril and famotidine caused significant reduction in ulcer index and gastric acid secretion (p<0.01) when compared to saline control group. Both of them did not show any effect on mucus content and surface tension of gastric juice. Concurrent administration of ibuprofen reduced the anti-ulcer effect of captopril significantly (P<0.01) and nullified the acid secretion inhibitory effect of captopril. However, the anti-ulcer and acid secretion inhibitory effects of famotidine were not altered by pretreatment with ibuprofen. Conclusion: Captopril may act through prostaglandins to inhibit gastric acid secretion and this effect of captopril on acid secretion may be the mechanism involved in its anti-ulcer effect.

0bjective:To study the gastric antiulcer effect of low doses of calcium channel blockers (CCB) namely, nifedipine, verapamil and diltiazem on potentiation of antiulcer and antisecretory effect of famotidine by them. Methods: Gastic ulcers were induced in rats by restraint, aspirin treatment and pyioric ligation.The ulcer score, volume of secretion and pH were recorded. Results: Nifedipine (200 'g/100 g) and verapamil (1 mg/100 g) produced a significant reduction in the ulcer score. However, diltiazem at a dose of 600 'g/100 g did not produce any effect on the ulcer score. All the three CCBs potentiated the antiucler and antisecretory effect of famotidine at doses which were ineffective in reducing the gastric ulceration when given alone. Conclusion: Nifedipine and verapamil offered a protective effect against gastric ulceration. Nifedipine, verapamil and diltiazem potentiate the antiulcer and antisecretory effect of famotidine at low doses. Based on these findings it may be speculated that the dose of famotidine could be reduced in patients receiving CCBs.

Objective: To investigate the antidepressant effect of selective alpha2-adrenoceptor blockade in mice. Methods:The study was done in Laka mice employing forced swimming-induced despair behaviour as test model. They were acutely treated with dose of 0.25, 0.5, 1 and 2 mg/kg, SC and effect of 1 mg/kg of idazoxan was seen at different time intervals of 15,30, 60 and 120 min.The reversal of effect of idazoxan by reserpine (2 mglkg, ip), isoprenaline (8 mg/kg, ip) and clonidine (0.15 mglkg, ip) was also studied. The antidepressant effect of idazoxan (1 mgikg) was compared with imipramine (10 mg/kg, ip) and fluoxetine (10 mg/kg, ip) in acute study and with imipramine (10 mglkg, ip) in chronic study. Duration of immobility in seconds during the 6 min test session was recorded and used to assess the antidepressant effect. Results: ldazoxan produced antidepressant effect in a dose dependent manner with maximum effect observed at 30 min. Prior administration of idazoxan (1 mg/kg) reversed isoprenaline- and clonidine-induced increase in immobility time. Further, the chronic idazoxan treatment (1 mg/kg x 9 d) reversed isoprenaline-induced despair behaviour but the effect was not statistically significant. Also the dose of 0.5 and 2 mgikg of idazoxan did not reverse clonidine (0.15 mg/kg) induced increased immobility time. ldazoxan also reversed reserpine (2 mg/kg) -induced despair behaviour after 4 h and 24 h. In acute study, idazoxan (1 mg/kg) produced significant and better effect as compared to imipramine and fluoxetine. The chronic effect of idazoxan was also more pronounced than chronic imipramine treatment. Conclusion: The results of the present study indicate involvement of presynaptic alpha2-adrenoceptors in the antidepressant effect of idazoxan.

0bjectives:To study the effect of Abana, an ayurvedic herbomineral preparation on blood pressure and vascular reactivity to noradrenaline (NA), acetylcholine (ACh) and isoprenaline (Iso) in normotensive control and ethinyl estradiol (EE)-induced hypertensive rats. Methods: Animals were divided into six groups receiving different treatments consisting of vehicle, EE (1.5 mg/kg/day i.m.) and Abana (3 g/kg/day orally) either alone or in combination for 3 or 6 weeks. After completion of the treatment schedules, effect of ACh, NA and Iso on the blood pressure and vasopressor effects of NA on the hindquarter preparation was studied. Dopamine-(-hydroxylase (DBH) activity was also measured in adrenal glands after completion of the different treatments. Results: Abana treatment for 3 weeks to normotensive rats produced significant lowering of blood pressure, enhancement of vasopressor response to low dose of NA (0.5 'g/kg IV). However, DBH activity of the adrenal glands and vasodepressor responses to ACh and Iso were not altered in Abana-treated rats. Combined treatment with Abana and EE for 3 weeks or pretreatment with Abana for 3 weeks followed by the combined treatment prevented EE-induced hypertension and increased the DBH activity of the adrenal glands. Also the altered vascular reactivity to NA (0.5 'g/kg IV) observed in EE-treated and Abana-treated groups were abolished in the groups receiving the combined treatments. Conclusion: It is suggested that Abana produced protective effects against EE-induced hypertension in rats probably by its sympathetic blocking property.

Objectives: To survey the variation in prices of drugs used in the management of cardiovascular diseases in the Indian market. Method: A review of drug prices mentioned in the July- September (1997) edition of Drugs Today was done. The retail cost of a drug being manufactured by different companies in the same strength, dosage form and number was compared. Results: A total of 84 formulations were compared. Variation in prices of all the drugs was observed and it ranged from 2.8% to 3406%. It was observed that greater was the number of companies manufacturing the drug, more was the variation in prices. Conclusion: The results of this study indicate that there exists a wide variation in prices of drugs manufactured by different companies. In the absence of comparative information on drug prices and their quality it is difficult for physicians to prescribe the most economical treatment. There is an urgent need to provide adequate information to physicians regarding cost, bioequivalence and quality of drugs.

Objective: To analyse the pattern of prescribing habits of doctors attached to a government teaching hospital and the general practitioners in Pondicherry. Methods: Prescriptions from government teaching hospital (n=162) and retail medical stores (n=149) from general practitioners were collected at random over a period of two months and the data were analysed on the following parameters - a) total number of drugs prescribed, b) generic vs brand, c) total parenteral drugs prescribed, d) fixed dose combinations and e) most commonly prescribed drugs. Results: Among the types of drugs used, antimicrobial agents were prescribed maximum in the government teaching hospital (26.9%) as well as by the general practitioners (23.7%). Analgesics, antiulcer drugs, vitamin preparations were the commonly prescribed agents by the general practitioners while topical medications, analgesics, antihistamines, and bronchodilators were the commonly prescribed drugs by the government doctors. General practitioners prescribed glucocorticoids, anabolic steroids, zinc with vitamins or vitamin E which were expensive, ineffective or may be harmful. lnjectables were also more frequently prescribed by them. Interestingly the prescriptions of government teaching hospital were more rational since the prescribers used fewer number of drugs in average and more frequently in their generic names. Conclusion: This study may help to identify the problems involved in therapeutic decision making and improve the prescribing behaviour by planning for an interventional strategy.