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IDPH-791, a new central muscle relaxant, produced dose dependent hypothermia in mice. The possible mechanism involved in this response was investigated. Adrenergic blocking agents (prazosin, phenoxybenzamine, yohimbine and propranolol), dopaminergic antagonist (haloperidol), serotonergic antagonist (methysergide) and antihistamines (mepyramine and cimetidine) did not cause any significant modification of the hypothermia. Similarly prostaglandin synthesis inhibitors (ketoprofen, indomethacin and paracetamol) also did not alter the hypothermia induced by IDPH-791, thus ruling out the possibility of central prostaglandin involvement. Atropine reversed the hypothermic response and physostigmine potentiated it, suggesting the possible involvement of acetylcholine acting through muscarinic receptors. There was also significant increase in total acetylcholine content of rat brain on pretreatment with IDPH 791. It is concluded that central muscarinic receptor may be involved in the hypothermic response of IDPH-791.

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Effects of lead (Pb) on 5-hydroxytryptamine (5-HT) induced contractions of isolated rat ileum and its modification by magnesium (Mg++) and reserpine were studied. Preparations incubated in Mg++ free or excess Mg++media showed supersensitivity and subsensitivity to 5-HT respectively. Reserpinization failed to induce supersensitivity to 5-HTin any Mg++ concentration of the medium, but in Mg++ free with ethylene diamine tetra acetic acid (EDTA) showed increased sensitivity to 5-HT. The inhibition observed with Pb in Mg++ with EDTA was comparatively less in both non-reserpinized and reserpinized preparations. Pb reduced the sensitivity and decreased the maximal responses to 5-HT in all Mg++ concentration of the medium tested.

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A study was carried out to find out the therapeutic implications of the tolbutamide - ketoconazole interaction in diabetic rabbits. Ketoconazole treatment (20 mgkg, oral once daily for one week) significantly increased and prolonged the antidiabetic effect of tolbutamide (40 mg/kg, oral) in diabetic rabbits. The AUC0-( and the terminal half-life of tolbutamide were increased significantly by ketoconazole indicating the decrease in its hepatic metabolism.

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Compound 3-cyano-4-methyl-5-vinyl pyridine (compound 89/62) produced a dose dependent (3-12 mg/kg, p.o.) choleretic activity in rats and significant anticholestatic activity (38-l00%) against paracetamol induced cholestasis. It also increased the viability of hepatocytes as assessed by trypan blue exclusion and oxygen uptake tests, Paracetamol induced biochemical changes in serum and isolated hepatocytes were normalised by the pretreatment with this compound.

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Amiodarone was reported to elevate the serum levels of several drugs including digoxin, flecainide, quinidine, phenytoin and warfarin. The effect of amiodarone on the pharmacokinetics and hypoglycaemic activity of tolbutamide was studied initially in a rabbit model to find out the possible drug interaction such that the clinical relevance can be studied if necessary at a later stage. Amiodarone (100 mg/kg, oral once daily for one week) significantly increased the absorption rate constant, terminal half-life and AUC0-( of tolbutamide (40 mg/kg, oral) in normal rabbits. The hypoglycaemic activity of tolbutamide was also enhanced and prolonged sig-nificantly in amiodarone treated rabbits. It appears that amiodarone increased the absorption and decreased the hepatic metabolism of tolbutamide in rabbits. Further studies are needed to find out the clinical relevance of this tolbutamide-amiodarone interaction observed in rabbits.

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The present investigation explored the possible toxinological effects of the Bidder's organ extract (BO-extract) of the toad Bufo melanostictus (Schneider) on experimental animals. The LD50 of the BO-extract was found to be 12.5 mg/kg (i.v) in male albino mice. BO-extract, produced significant fall of body temperature in male normothermic albino mice but not in hyperthermic male albino rats. Pentobarbitone-induced sleeping time was significantly potentiated in mice. Bo-extract produced hypertensive action on cat and rat blood pressure which was totally antagonised by a-adrenergic blocker. On isolated heart, BO-extract initially in-creased the rate of contraction and finally produced irreversible cardiac arrest. On isolated guinea pig auricle, it also produced irreversible blockade of contraction. BO-extract significantly increased cutaneous capillary permeability in guinea pig and produced vasoconstrictor effect on rat hind-quarter perfusion. It produced quick contractile response on isolated guinea pig ileum, an action antagonised by cyproheptadine. At lower dose BO-extract potentiated the electrical stimulation induced twitch response on isolated rat phrenic nerve diaphragm and chick biventer cervicis and at higher doses it produced irreversible blockade of chick biventer cervicis muscle. BO-extract did not possess haemorrhagic activity but possessed strong haemolytic activity on washed goat RBC (HD50= 150 'g).

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Seventy six bottles of 19 different brands of anti- glaucoma eye drops (pilocarpine 1, 2, 4 % and timolol 0.25, 0.5 %) were tested for total volume, total number of drops, drop volume, drops/ml, and duration of therapy, by using a 10 ml glass cylinder with 0.1 ml graduations and a mechanical counter. The range of the drop volume for pilocarpine 1% was 55.3 - 55.4 'l: pilocarpine 2% was 41 .O - 54.4 'l; pilocarpine 4% was 47.8 - 47.8 'l and timolol 0.25% was 38.7 - 55.2 'l; timolol 0.5% was 35.9 - 55.6 'l. Ten out of 19 brands of antiglaucoma eye drops had total volume less than the labelled amount. The drop volume of the commercial anti- glaucoma eye drops is more than optimal.

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In the present study, the effect of single dose administration of 4 mg lorazepam on psychomotor performance was demonstrated in 6 volunteers. Performance was measured using a battery of paper and pencil tests which included B-letter cancellation test, digit symbol substitution test, symbol copying test, serial addition and serial subtraction tests, All the tests were sensitive to detect the lorazepam induced impairment of psychomotor function. This can be used as a model experiment to demonstrate to the undergraduate medical students the effects of CNS depressant drugs in humans. The student can also become acquainted with the concepts of clinical pharmacology during the demonstration.

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The effects of intracerebroventricularly administered (ICV) FMRFamide (Phe-Met-Arg-Phe-NH2 ) were investigated on the locomotor activating properties of morphine (2.5 mg/kg, SC) and d- amphetamine (0.5 mg/kg, SC) in rats. FMRFamide (0.1 - 10 'g) had no effect of it's own, but antagonised morphine and amphetamine stimulated locomotion. The data suggests that FMRFamide through modulation of central opiate system decreases the behavioural activation produced by morphine and amphetamine.

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Effect of calcium channel blockers on glucose tolerance in normal rats was studied. Nifedipine, verapamil and diltiazem produced no significant change in blood glucose level in normal rats. But pretreatment with these calcium channel blockers raised the glucose level significantly in rats after glucose load and adrenaline injection. It is concluded that calcium channel blockers have no significant effect on basal insulin release but possibly inhibit its release when body demands an extra release of insulin to maintain homeostasis.

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