Between that tragic incident at Bhopal and now, much progress has been made to understand the systemic effects of methyl isocyanate (MIC). Being a potent pulmonary irritant, inhaled MIC causes respiratory depression and extensive alveolar damage. In spite of its high reactivity, MIC either inhaled or administered through systemic route reaches various organs in its active form and produces a dose dependent hypotension, haemoconcentration, hyperglycemia, clinical lactic acidosis and uraemia in rats. The sequence of events after MIC intoxication subcutaneously clearly indicates the primary event to be hypotension, persisting for a longer duration with increasing severity possibly due to fluid loss (hypovolemia). However, the predominant biological effect of MIC intoxication in mammals is severe tissue hypoxia leading to acute metabolic acidosis, The raison d'etre for the induction of tissue hypoxia by MIC are many fold. Besides, the respiratory depression, MIC causes stagnant hypoxia affecting cardiovascular system and histotoxic hypoxia through its effects on the mitochondrial respiration Apart from the acute necrotizing bronchiolitis due to corrosive action of MIC, the histological changes such as the severe intraseptal edema, collection of fluid and exuded plasma proteins within the interstitial and alveolar spaces and those observed in the other vital organs provides clear evidence for the occurrence of fluid loss from the vascular compartment leading to hypovolemic shock.

Effects of acute and chronic administration of '- and k-opioid receptor agonists, morphine (MOR) and ketocyclazocine (KCZ), on food intake and their interaction with neuro-hypophysial neuropeptide, argininea8-vasopressin (AVP) have been investigated in rats. After single administration both MOR and KCZ (1 'g/rat, icv) enhanced food intake, measured for 6 h during the light phase. The responses were reversible by respective antagonists, naltrexone and Mr2266. However, after chronic administration the responses were differentially modified, i.e., there was a further enhancement of hyperphagic effect of MOR, whereas tolerance developed to this response of KCZ. AVP (0.1 'g/rat, icv) per se, did not significantly affect the food intake response. However, pretreatment with AVP attenuated the hyperphagic response to single administration of MOR or KCZ. On chronic treatment AVP (a) blocked the accentuation of hyperphagic response to MOR and (b) facilitated the attenuation of hyper-phagic response to KCZ.Results are discussed in the light of complex opioid - AVP interaction during food intake in rats.

Development of behavioural tolerance to the organophosphate insecticide, monocrotophos was assessed in male albino rats. Development of tolerance was indicated by the disap-pearance of most of the signs of toxicity and the onset times of recovery in body weights, food and water intake. The signs of toxicity were mainly cholinergic. Tolerance occurred despite continued inhibition of striatal acetylcholinesterase (AChE) activity throughout the period of investigation (16 days). The degree of AChE inhibition, however, was progressively reduced upto 16 days which could be attributed to de novo synthesis of AChE. The doses of 4.5 and 6.0 mg/kg/day were found to be effective in inducing behavioural tolerance during 16 days of daily treatment. The present study indicates that continued exposure to monocrotophos decreases the body weights and intake of food and water, and tolerance develops to this inhibition and behavioural effects in due course.

Basic amide hydrochloride compounds were found to be potent local anesthetics (100% potency), with onset of action comparable with lignocaine. Within a series, duration of anesthesia was found to increase with the increase in hydrocarbon chain length attached to "thio" moiety. Compounds B to E and H which were found to be potent local anesthetics, also possessed potent vasoconstrictor activity. The correlation coefficient between vasoconstridor activity and duration of local anesthetic activity was found to be 0.6. The Ld50 values as determined by acute toxicity studies in mice was greater than 22.4 mg/kg. Our data suggest that basicamide HCI compounds with "thio" moiety possess local anesthetic agent of greater potency and duration.

Tephrosia purpurea, known as Sarapunkha in Ayurveda for its hepatoprotective action, was evaluated for its efficacy in rats by inducing hepatotoxicity with D-galactosamine HCI (acute) and carbon tetrachloride (chronic). Tephrosia purpurea (aerial parts) powder was administered orally at a dose of 500 mgkg. Serum levels of transaminases (SGOT and SGPT) and bilirubin were used as the biochemical markers of hepatotoxicity. Histopathological changes in the liver were also studied. The results of the study indicated that the administration of Tephrosia purpurea along with the hepatotoxins offered a protective action in both acute (D- galactosamine) and chronic (CCl4) models.

Effects of twice daily administration of a beta-agonist terbutaline on body composition of growing Wistar rats were evaluated in well nourished (WN) male pups of small litters and compared with pre-weaning nutritionally deprived (PND) pups of large litters. Carcass analysis at 21 days of age showed increased cardiac weights in WN pups on terbutaline treatment. The lipid content of treated rats, both WN and PND, were significantly reduced with no changes in the total protein content of the carcass. Non-specific beta-agonists like terbutaline influence the lipid and not the protein content of both well-nourished and undernourished growing male rats.

After 15 days of single daily oral administration of tricyclic antidepressants (imipramine, desipramine 10 mg/kg each, amitriptyline, nortriptyline 7.5 mg/kg each and protriptyline 5 mgikg) in rabbits, reduced the minimum effective dose of gallamine to elicit head drop. Potentiating effect persisted significantly up to 24 hour. Similarly double the doses of these tricyclic antidepressants reduced the quantity of gallamine significantly up to 48 h. and total recovery from the effect appeared after 72 h. It is suggested that the potentiation of the action of gallamine by tricyclic antidepressants may be of clinical importance in patients especially if any of these tricyclic antidepressants has been taken shortly before.