The new information super highway is the Internet. The basic facilities of the Internet, at present, available in India are Electronic mail, World Wide Web, File Transfer Protocol, Telnet and Internet Relay Chat. The Internet can be used for electronic conferencing, subscribing to mail servers, browsing many journals, free Medline search, obtaining teaching materials / computer software and seeking for jobs and fellowships. An outline of the procedure for Medline search on the Internet is given. Some of the interesting Website addressess of pharmacology journals and associations are provided. Finally, the minimum requirement of hard- ware and the procedure for obtaining Internet connection in India is explained.

The endothelin family of peptides are very potent endogenous vasoconstrictor and pressor agents, secreted by various cells and tissues in the human body. Of the 3 isoforms, endothelin is the major isoform produced by the vascular endothelium. Two endothelin receptor subtypes have so far been cloned in mammalian species, ETA and ETB. Since their discovery in 1988, the endothelins have been the subject of intense research on their physiological function and potential pathophysiological role in various disease states. There is now good evidence that endothelin regulates vascular tone and blood pressure and is important in the regulation of various functions like pulmonary, endocrine, central nervous system and foetal development. Studies with endothelin receptor antagonists have underlined the important role of endothelins in various disease states like chronic heart failure, hypertension, bronchial asthma, subarachinoid haemorrhage, vasospastic disorders and some developmental disorders. There are now a number of selective ETA and combined ETA/B receptor antagonists available for preclinical studies. Some of these agents are currently being assessed in early phase clinical trials. However, it is still not clear which of these will prove to be of most therapeutic value.

Objective: To assess whether chronic rafoxanide adminstration would cause sensitisation or tolerance like other reported neuroleptic drugs to various behavioural and physiological parameters and colonic temperature to rats. Methods: The study was done in adult male Sprague Dawley rats. They were chronically treated with rafoxanide in the doses of 1,3 and 10mg/kg i.p. for 3 weeks, and control animals received saline. Challenges of phencyclildine (PCP) 1, 3 and 10 mg/kg i.p. on day 17, amphetamine 5mg/ml on day 19 and apomorphine 1 mg/ml on day 21 were administered. The following parameters were studied during chronic administration of rafoxanide and after giving the challenges: (a) behavioural (catalepsy, locomotor activity, stereotypies and colonic temperature change) and physiological parameters (body weight, food and water intake). Results: Chronic administration of rafoxanide had no effect on body weights, food, water intake and on catalepsy, while saline challenge to chronically treated rats 3 and l0mg/kg group showed a significant decrease in total activity. PCP challenge produced significant increase in total activity in all 3 groups (1, 3 and 10 mg/kg) chronically treated animals, whereas, amphetamine challenge had no effect on total activity in these animals. Apomorphine challenge produced a significant decrease in total activity in all groups of chronically rafoxanide treated animals. All challenges produced no change in behaviour except PCP challenge which produced significant effects on rolling behaviour which was increased in all the 3 groups. Chronic rafoxanide and saline had no effect on colonic temperature, while apomorphine challenge produced significant reduction in colonic temperature for all 4 groups of animals (saline group, rafoxanide groups of 1, 3 and 10 mg/kg). Conclusion: Chronic rafoxanide treatment neither induced catalepsy nor DA-receptor sensitisation as indicated by changes in colonic temperature, behavioural and physiological parameters.

Objectives: To elucidate the mechanism of anticonvulsant action of sepia shell (cuttle bone) extract against pentylenete- trazole (PTZ) induced seizures in mice. Methods: The powdered shells were subjected to acid and alkali extraction followed by dialysis. The dialysate was administered intraperitoneally to Swiss albino mice at a dose of 600 mg/Kg to study the anitconvulsant action. Seizures were induced by PTZ at a dose of 80 mg/Kg, adminsitered intraperitoneally. The brains from the control and test groups were removed immediately after cervical dislocation and placed in dry ice. The monoamines, i.e., serotonin, dopamine and noradrenaline were estimated fluorimetrically. Results: Shell extract per se did not influence the serotonin levels in brains. When PTZ alone was administered, there was a significant decrease (10.45%) in serotonin content with respect to controls. In the group treated with sepia shell extract (SSE)+ PTZ, the brain levels of serotonin were found to be very high (72%) similar to that observed in phenytoin per se treated group. Catecholamines were not significantly affected by any of the treatments. Conclusions: The anticonvulsant action of sepia shell extract may be due to the elevation of the seizure threshold rather than the prevention of seizure spread, as SSE was able to abolish the clonic as well as tonic stages of the convulsions. This action is probably mediated by the increased serotonergic transmission rather than catecholaminergic.

Objects: To test the antimutagenecity of water alcoholic and oil extracts of Semecarpus anacardium. Methods: Water, alcoholic and oil extracts were prepared and tested in the bacterial test system using Salmonella typhimuriurn strains TA96 and TA100 in the presence and absence of metabolic activities. The antimutagenecity was tested versus Benso(a)pyrene (BzP) in dose dependent manner. Alcoholic and water extracts were also tested in human lymphocyte in vitro for its antimutagenic activity versus BzP at concentration of 1OOO'g per tube. Results: The water, alcoholic and oil extracts of Semecarpus anacardium were antimutagenic versus BzP in a dose dependent manner. The water and alcoholic extracts were antimutagenic versus BzP induced micronuclei at concentrations of 1OOO'g per tube in human lymphocytes. Conclusion: Water, alcoholic and oil extracts of S. anacardium are antimutagenic against BzP induced mutagenecity.

Objective: To study the anti-inflammatory effect of G. asiatica root in male albino rats. Methods: Carrageenan-induced rat paw oedema (acute inflammation) and cotton pellet granuloma (chronic inflammation) methods have been used. Results: G. asiatica root powder was effective in reducing the oedema during the various phases of acute inflammation. In chronic phase the weight of cotton pellet granuloma was also reduced by G. asiatica treatment. G. asiatica also reduced the lipid peroxide content of granuloma exudate and liver, (-glutamyl transpeptidase in the granuloma. Serum albumin in granuloma was normalised. G. asiatica also normalised the increased levels of serum acid and alkaline phosphatase. Conclusion: The crude drug may exert anti-inflammatory activity by anti-proliferative, anti-oxidative and lysosomal membrane stabilisation

Objective: To investigate the effect of metoprolol (cardioselective beta blocker), prazosin (alpha blocker) alone and in combination on reperfusion induced arrhythmias in intact rabbit hearts. Methods: Newzealand white rabbits of either sex weighing 1.5 to 2 kg were used. The coronary artery was ligated for 30 minutes and then reperfusion was carried out for 60 minutes. Metoprolol alone (0.5 mg, 0.75 mg and 1mg/kg B.wt.), prazosin alone (0.25 mg, 0.5 mg and 1mg/kg B.wt.) and combination of lowest dose of metoprolol (0.5 mg/kg) and prazosin (0.25 mgkg) was administered intravenously at the time of reperfusion in different groups of animals. Electrocardiogram was monitored every 5 minutes using limb lead II throughout the experiment. Incidence and severity of arrhythmias were analysed from ECG recordings. Results: Metoprolol in all doses produced slight bradycardia and percent protection against arrhythmias was 0 to 16.6% with different doses.Percent protection produced by prazosin was 33.3 to 66.6%. When metoprolol (lowest dose) was used in combination with prazosin (lowest dose) there was no change in heart rate and percent protection against arrhythmias was 83.3%. Conclusion: Combination of a cardioselective beta blocker (metoprolol) and an alpha blocker (prazosin) has produced potentiation of effect in protecting the heart against reperfusion induced arrhythmias in intact rabbit heart.

Objective: To evaluate the safety and efficacy of lovastatin in comparison with gemfibrozil in 60 Indian patients with primary hypercholesterolemia (250-350 mg/dL). Methods: After excluding patients with exclusion criteria, 60 adult patients were randomly allocated to the study medication which contained either lovastatin tablets 20 mg or gemfibrozil capsules of 300 mg for 4 weeks and the lipoprotein profile was estimated before and after the treatment. Results: Of the 60 patients, only 44 were available for efficacy analysis, 18 in gemfibrozil group and 26 in lovastatin group and the rest were drop outs. There was a statistically significant reduction in LDL cholesterol from base line value in lovastatin group (32.8%) in comparison with gemfibrozil group (20.35%). Lovastatin was better in raising HDL cholesterol from the base line value (16.3%) in comparison with gemfibrozil (-1.7%) Although there was better reduction in total cholesterol and triglycerides with lovastatin group, this was statistically not significant. Gastrointestinal side effects severe enough to warrant drug withdrawal occurred only in 3.3% (n=1) of lovastatin group as against 33.3% (n=9) of gemfibrozil group. Conclusion: Lovastatin is superior to gemfibrozil in lowering LDL cholesterol and raising HDL cholesterol and it is better tolerated.

Objective: To see the efect of anti-stress agents like Panax ginseng and diazepam on stress-induced elevation of 5-hydroxytryptamine (5-HT) in brain and hypothalamus of rats. Methods: 5-HT was estimated in brain and hypothalamus of rats by spectrophotofluorometry with simultaneous fluorimetric estimation of corticosterone as an index of activation of hypothalamo-hypophyseal- adrenal axis. Results: Panax ginseng and diazepam both per se did not modify brain and hypothalamic 5-HT in unstressed rats. But both of them attenuated stress-induced elevation of brin and hypothalamic 5-HT. Conclusion: Mediation of 5-HT in anti-stress effect of Panax ginseng and diazepam can not be conjectured, as they may have a non specific anti-stress effect.

Objective: To investigate certain haematological and biochemical changes following 90 days administration of pendimethalin in rats. Methods: Eighteen female rats were randomly divided into three groups. While one group served as control,the remaining two were administered pendimethalin at the dose rate of 24 and 48 mg/kg/day, orally once daily for 90 days. On day 46 and 91. all the animals were anaesthetized and blood samples were collected to study some haematological and biochemical profiles. Also, three rats from each group were sacrificed on day 91 to record the relative organ weights. Results: Administration of pendimethalin (24 or 48 mgikg) did not produce any apparent signs of toxicity or mortality. However, it caused marginal reduction in haemoglobin (Hb), total erythrocyte count (TEC), significant (P<0.05) elevation in plasma cholesterol level and relative weights of liver and adrenals at higher dose. Pendimethalin did not cause any appreciable changes in total leucocyte count (TLC) and absolute lymphocyte count (ALC), plasma proteins, glucose and blood urea nitrogen (BUN) concentrations; and,alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities. Conclusion: Administration of pendimethalin for 90 days exerts mild haemotoxic effect and probably interferes with lipid metabolism.

. Forty healthy individuals and 70 psychiatric patients aged 25 to 45 years without previous history of TAB inoculation or enteric fever during last one year and serum negative for S. typhi and S. paratyphi (A & B) antibodies (titre<40) were selected. Group of 40 healthy individuals served as control. The psychiatric patients were started on chlorpromazine 2.5 mg three times a day orally. On 7th day 1 ml of formalised TAB vaccine (Glaxo) was injected subcutaneously. Blood was with-drawn on 15th and 30th days of inoculation and serum was tested for antibody titre by agglutination. The antibody titre was significantly lower in the chlorpromazine treated group against TO and TH on 15th day and against PA (H) and PB (H) also on 30th day. The parallel shift of the curves in the treated group as compared to the control suggests that only one mechanism is likely to be responsible for the reduction in antibody titre. It is concluded that chlorpromazine produces a significant immunological inhibition when administered for 7 days prior to TAB vaccine.

Ayurveda has quite a sophisticated classification of medicinal plants, as per the dominant pharmacological/ therapeutic activity on mental functions etc. These need to be systematically evaluated by a multidisciplinary effort. The most interesting leads of CNS-active medicinal plants, which have emerged, besides Rauwolfia serpentina are (1) Mucuna pruriens for Parkinson's disease (2) Withania somnifera, as anxiolytic (3) Centella asiatica and Bacopa monniera for learning and memory disorders (4) Acorus calamus as anxiolytic and (5) Ocimum sanctum as an antistress agent. The interface of molecular psvchiatrv and the active principles of some of these plants will be a major field for new developments in neuropharmacology and CNS-active drugs.

: Japanese herbal medicine (Kampo medicine) is a well-established remedy with a long history which is especially useful in treating chronic diseases and psychosomatic diseases. Recently not only its safety but its efficacy is re-evaluated with its possibility to improve such difficult diseases as senile dementia. In this paper, history, clinical use, and fundamental philosophy of Kampo medicine are reviewed along with the results of recent clinical studies.

Ayurvedic literature describes psychotropic properties of many herbs. In recent years they have been evaluated for efficacy and safety by using modern methods of human pharmacological investigations. The article describes the observations of the authors while conducting clinical trials of some of the compounds claimed to have psychotropic properties.

The preventive effect of the Japanese herbal medicine "Boui-Jiou-Tou (BJT)" on senility using Senescence Accelerated Mouse (SAMP 1 TA/Ngs), which is considered to be useful models of human ageing in some respects. The investigation of the effects of herbal medicine on the behaviour, learning ability, longevity and histological changes in this animal model may be important for basic studies on ageing in humans. Pellet feed containing 0.052% BJT was given to the treated group, consisting of 25 mice, ad libitum from the age of six weeks, for twenty-four weeks. Learning ability was assessed, and spontaneous motor activity was measured. A histological examination was carried out. The longevity of mice was also assessed. In the passive avoidance task, the period until acquisition of standard achievement rate was 3 days shorter in the treated group than in the control group. The mean number and density of dendritic spines were higher in the treated group than in the control group. With regard to life span, median survival time tended to be longer in the treated group (54 weeks) than in the control group (41 weeks). The results of this study suggest that BJT indeed exerts some valuable effect in the prevention of learning disturbance and senility.

Bacopa monniera Linn. (Brahmi) has been used since times immemorial as nerve tonic for Improvement of memory The authentication of the traditional claims of brahmi was initiated by investigating the effect of an alcoholic extract of this plant on acquisition, consolidation and retention of three newly acquired behavioural responses in albino rats, viz.. a foot-shock motivated brightness discrimination response, active conditioned avoidance response and Sidman continuous avoidance response. The facilitatory effect of the brahmi extract (40 mg/kg, p o. x 3d) was manifest in all the three learning responses as it augmented both the cognitive function and mental retention capacity. The chemical constituent responsible for the facilitator) effect of brahmion learning schedules was identified as a mixture of two saponins designated as bacosides A and B.The bacosides significantly improved the acquisition, consolidation and retention in the shock-motivated brightness discrimination response, active conditioned avoidance response and produced a dose-dependent facilitation of discretion between an aversive (LiCL) and palatable fluid (sucrose) in the conditioned taste aversion (CTA) response. Bacosides also attenuated the retrograde amnesia produced by Immobilisation induced stress, E C S and scopolamine. They also enhanced protein kinase activity and produced an Increase in protein in hippocampus. Bacosides were also found to be safe in regulatory pharmacological and toxicological studies and were well tolerated by normal healthy male human volunteers in single dose (20-300 mg) and multiple doses (100 and 200 mg) administered for 4 weeks double blind placebo controlled and non-crossover regulatory Phase-I clinical trial.

Cycleanine, an alkaloidal extractive from the root bark of Synclisia scabridav, was screened for some peripheral and central effects in addition to acute toxicological investigation. The intraperitoneal LD50 in mice was established as 1010.5 mg/kg. In vivo studies using mice revealed that cycleanine significantly reduced spontaneous motor activity (SMA) in a dose related manner. There was synchronization of EEG and activation of EMG. In vitro studies using isolated rat uterus showed that cycleanine evoked concentration dependent contractions that were resistant to atropine but blocked by salbutamol. These results help to explain the rationale for the folkloric use of the plant in various CNS and peripheral disorders, and also implicate cycleanine as the putative active component.