Calcitonin gene-related peptide (CGRP), a 37 amino acid neuropeptide, identified in multiple species, has widespread distribution and expression. CGRP acts through G protein-coupled receptors whose presence and changes in function modulate the peptide's effects in various tissues. Three receptor subtypes have been identified and CGRP's signal transduction through the receptors is dependent on two accessory proteins: Receptor activity modifying protein1 (RAMP1) and Receptor component protein (RCP). Several endogenous substances such as glucocorticoids, nitric oxide (NO), nerve growth factors (NGF), and steroid hormones modulate CGRP release and synthesis. Both peptide and non-peptide agonists and antagonists of CGRP receptors are being developed. Also the therapeutic benefits of some antagonists such as BIBN 4096 BS in migraine have been promising. This brief review provides a preliminary understanding of the diverse biological effects of the peptide in various systems. The current status of CGRP and its receptors in many pathophysiological states is not fully explored and future findings are greatly awaited.

OBJECTIVE: To evaluate the potential efficacy of Glycyrrhiza glabra Linn. (Fabaceae) in protecting tissues from peroxidative damage in CCl4-intoxicated rats. MATERIAL AND METHODS: Peroxidative hepatic damage in rats was studied by assessing parameters such as thiobarbituric acid reactive substances (TBARS), conjugated dienes (CD), superoxidedismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), glutathione peroxidase (GSH-Px) and glutathione (GSH) in liver and kidneys. The effect of co-administration of G. glabra on the above parameters and histopathological findings of the liver in experimental animals was studied. RESULTS: The increased lipid peroxide formation in the tissues of CCl4-treated rats was significantly inhibited by G. glabra. The observed decreased antioxidant enzyme activities of SOD, CAT, GSH-Px, GST, and antioxidant concentration of glutathione were nearly normalized by G. glabra treatment. Carbon tetrachloride-induced damage produces alteration in the antioxidant status of the tissues, which is manifested by abnormal histopathology. G. glabra restored all these changes. CONCLUSION: Glycyrrhiza glabra is a potential antioxidant and attenuates the hepatotoxic effect of CCl4.

OBJECTIVE: To evaluate the preliminary antiimplantation activity of isolated pure principles from successive extracts of petroleum-ether (PE) and ethyl acetate (EAc) and subsequent crude alcoholic extract of seeds of T. populnea in female albino rats. MATERIAL AND METHODS: Graded doses of the active principles and the crude alcoholic extract (in 1% gum acacia suspension) were tested for possible antiimplantation activity in Sprague-Dawley female rats of normal estrus cycle after overnight cohabitation with males of proven fertility. The day when spermatozoa was detected in vaginal smear was treated as 1st day of pregnancy. The compounds were administered to female rats from the 1st day to the 7th day of pregnancy. On the 10th day, the rats were laparotomized under light anesthesia and the numbers of implantation sites and corpora lutea were noted. RESULTS: Chromatographic pure principle from PE extract showed significant antiimplantation activity (60 %) at the dose of 110 mg/kg, b.w while that from EAc extract showed 48.6 % effect at the same dose. In contrast, the final alcoholic extract showed no such significant action. CONCLUSION: The active principles from PE and EAc extracts showed significant antiimplantation activity and they were found to be a mixture of two groups of long-chain fatty acids from GLC.

OBJECTIVE: To study the clinical spectrum of cutaneous adverse drug reactions (ADRs) in hospitalized patients and to establish a causal link between the drug and the reaction by using WHO causality definitions. MATERIAL AND METHODS: A prospective hospital-based study over a period of one year (October 1, 2002 to September 30, 2003) was carried out by the Department of Pharmacology in the Department of Dermatology of St. John's Medical College Hospital. The cutaneous ADRs of in-patients admitted to the Department of Dermatology and in-patients transferred from other departments were recorded. The data were subjected to descriptive analysis. RESULTS: A total of 56 patients diagnosed to have cutaneous ADRs were included in the study. Only drugs having certain and probable causal association with the reaction were considered for analysis. One reaction had certain causal association while 45 patients fell into the category of probable association. The most common types of ADRs were maculopapular rash (35%), followed by toxic epidermal necrolysis (TEN) (20%) and Stevens-Johnson syndrome (SJS) (15%). The drugs implicated for cutaneous ADRs were antiepileptics (44%), chemotherapeutic agents (32%), NSAIDs (11%). Antiepileptics were responsible for causing the maximum number of maculopapular rash (56%), TEN (55%) and SJS (43%). The reaction times for all these reactions were in accordance with the previous reports that confirm the causality of the suspected drug. CONCLUSION: The occurrence of cutaneous ADRs in the present study was similar in many ways to studies conducted in India. A wide clinical spectrum of cutaneous ADRs ranging from mild maculopapular rash to serious SJS and TEN was observed. The incidence of life-threatening cutaneous ADRs like SJS and TEN was found to be higher compared to studies published abroad. Antiepileptics were implicated in the majority of the hospitalized cutaneous ADRs. Infrequently reported adverse reactions for newer drugs like leflunomide, cefotaxime and azithromycin were also detected in the present study.

OBJECTIVE: To evaluate the vulnerability of gastric mucosa to ulceration in non-insulin-dependent diabetes mellitus (NIDDM) rats vis-à-vis the protective effects of the methanolic extract of Pterocarpus marsupium heartwood (PMS, an antidiabetic herbal plant). MATERIAL AND METHODS: NIDDM was produced in 5-day-old rat pups by administering streptozotocin (70 mg/kg, i.p). The animals showing blood glucose level > 140 mg/dl after 12 weeks of STZ administration were considered as NIDDM positive rats. The effective hypoglycemic dose of PMS (750 mg/kg/day, p.o.) for 6 days was studied for its gastric ulcer (GU) protective effects against cold restraint stress (CRS), aspirin (ASP), ethanol (EtOH) and pylorus ligation (PL)-induced GU both in normal (NR) and NIDDM rats. To ascertain the mechanism of action, the effects of NIDDM and that of PMS treatment in NIDDM rats on mucosal offensive acid-pepsin, free-radicals (LPO,NO) and defensive mucin secretion, cell shedding, cell proliferation, glycoproteins and antioxidant enzymes (SOD and CAT) were studied. RESULTS: PMS (750 mg/kg) decreased the blood sugar level both in NR and NIDDM rats. NIDDM rats exhibited an increased propensity to GU, induced by CRS, ASP, EtOH and PL. Though, PMS did not protect the NR rats against GU induced by the above methods it reversed their increased propensity in NIDDM rats. NIDDM PL-rats showed an increase in acid-pepsin secretion, cell shedding and decrease in mucin secretion and mucosal glycoproteins with little effect on cell proliferation. PMS treatment in NIDDM rats reversed the acid-pepsin secretion, enhanced mucin and mucosal glycoproteins and decreased cell shedding without any effect on cell proliferation. NIDDM-CRS rats showed a significant increase in LPO and NO and a decrease in SOD and CAT levels, which were, reversed by PMS treatment. CONCLUSION: NIDDM increased the propensity to GU by affecting both offensive (increased) and defensive (decreased) mucosal factors. Though PMS, a hypoglycemic agent, did not show any protection against ulceration induced by CRS, ASP, EtOH and PL in normal rats, it protected the mucosa against the same in NIDDM rats by affecting the above mucosal offensive and defensive factors.

OBJECTIVE: To investigate the hepatotoxic effects of halofantrine in guinea pigs. MATERIAL AND METHODS: Halofantrine (30-105 mg/kg) was administered orally to three groups of guinea pigs thrice a week for 4 weeks. One group of animals which received distilled water served as control. The relative weight of the liver was measured. The biochemical parameters like alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and also total and conjugated bilirubin were measured. Liver tissues were subjected to histopathological examination. RESULTS: There was a significant (P<0.05) increase in the relative weight of the liver in all the treated groups compared to control. There was also a significant (P<0.05) increase in all the liver enzymes and total and conjugated bilirubin. Histopathological examination of the liver revealed moderate portal triaditis to severe hepatic degeneration in the halofantrine-treated groups. CONCLUSION: Halofantrine exhibits hepatotoxic effect in guinea pigs.

OBJECTIVE: To evaluate the acute adverse effects with respect to exploratory and spontaneous locomotor activity of mice produced by lamotrigine (LTG) alone or in combination with conventional antiepileptic drugs (AEDs) such as valproate, diphenylhydantoin, carbamazepine and phenobarbital. MATERIAL AND METHODS: Adult male mice were given an i.p. injection of LTG alone or in combination with conventional AEDs. When the maximum anticonvulsant activity of AEDs was at its peak, the exploratory and spontaneous locomotor activity of animals was electronically monitored. Three parameters (ambulatory activity, rearing activity and total distance traveled by animals) as indicators of the locomotor activity of the animals tested were electronically evaluated by means of the locomotor monitor system. RESULTS: The combination of LTG and valproate was devoid of any adverse effects on the locomotor activity. In contrast, the combination of LTG and carbamazepine drastically reduced the exploratory and spontaneous locomotor activity of animals in all analyzed parameters. Likewise, diphenylhydantoin combined with LTG also displayed the hypolocomotor effect as compared to the control animals. Phenobarbital either alone or in combination with LTG reduced the rearing activity. CONCLUSION: Combining LTG with valproate is advantageous because of a lack of any hypolocomotor effects, whilst the combination of LTG and carbamazepine leads to a drastic reduction in locomotor activity in animals. LTG combined with diphenylhydantoin produces a substantial decrease in the activity in mice, whereas phenobarbital alone exclusively reduces the rearing activity of the animals tested.