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Biomedical subjects

W G Clark

Publications and source records attributed to W G Clark.

At least 91 records · Page 5Linked to original sources
PubMed1975

The antipyretic effect of indomethacin.

1. Several possible mechanisms of the antipyretic action of indomethacin administered cat. 2. Indomethacin did not decrease bacterial endotoxin-induced release of endogenous pyrogen in vivo. 3. Indomethacin (5-40 mug/kg) inhibited the pyrogenic effect of peripherally or centrally administered leucocytic progen. A dose of 10 mug/kg caused a parallel shift to the right of the log dose-response curve for I.V. leucocytic pyrogen and reduced the potency of the pyrogen at least 50%. 4. Incubation of leucocytic pyrogen with indomethacin did not alter its pyrogenic potency. 5. Indomethacin exerted only a slight non-dose-related hypothermic effect in afebrile animals. 6. Indomethacin (up to 1 mg/kg) did not diminish the hyperthermic response to intraventricular administration of prostaglandin E1. 7. This pattern of activity indicates that indomethacin acts centrally to inhibit an effect of leucocytic pyrogen.

Animals↗
PubMed1975

Blockade of the central effects of d-amphetamine by amantadine. II.

1-Adamantanamine (amantadine) pretreatment significantly reduced the motor hyperactivity and hyperthermia caused by d-amphetamine in reserpinized mice. In drug-naive mice, when amantadine was administered after d-amphetamine, the motor activity caused by the latter also was decreased. Since our earlier studies showed that amantadine pretreatment also antagonized the increases in both motor activity and homovanillic acid (HVA) in the caudate nucleus caused by d-amphetamine in mice, it is suggested that the antagonism is due to a competitive blockade at the pre-synaptic level in the brain.

Amantadine↗
PubMed1974

Complementary lowering of the behavioural and physiological thermoregulatory set-points by tetrodotoxin and saxitoxin in the cat.

1. Injections of tetrodotoxin or saxitoxin (25 ng in 0.10 ml.) into a lateral cerebral ventricle caused deep body temperature of cats to fall approximately the same amount (2 degrees C) whether the animals were resting in the cold (4 degrees C) or were responding to escape heat.2. Continuous exposure to heat either prevented the hypothermic response or enhanced the level of tachypnoea required to lower body temperature. Tetrodotoxin also caused hypothermia when an animal was lever pressing to obtain heat in the cold environment.3. These results provide evidence that agents which alter the set-point for physiological thermoregulatory activity produce a complementary shift in the behavioural set-point as well.

Animals↗
PubMed1974

The hyperthermic effect of intracerebroventricular cholera enterotoxin in the unanaesthetized cat.

1. Cholera enterotoxin was used to evaluate a possible role of endogenous cyclic AMP in production of hyperthermia. Injection of purified toxin (0.10-1.0 mug in 0.10 ml.) into the lateral cerebral ventricle of unanaesthetized cats caused dose-related hyperthermic responses. Heating the toxin for 40 min at 90 degrees C abolished its hyperthermic activity.2. Intraventricular administration of dibutyryl cyclic AMP (250-1000 mug) also caused hyperthermia which, however, was preceded by transient periods of hypothermia and/or excitation in about half of the tests.3. Paracetamol, indomethacin and sodium salicylate inhibited hyperthermic responses to cholera enterotoxin. Paracetamol and indomethacin also inhibited hyperthermia induced by dibutyryl cyclic AMP (sodium salicylate was not tested).4. It is likely that the hyperthermic effect of cholera enterotoxin in the cat is mediated via endogenous cyclic AMP and that the antipyretics inhibit this effect by an action subsequent to the increase in cyclic AMP.5. It is unlikely that prostaglandin-induced hyperthermia in the cat is mediated via cyclic AMP since these antipyretics do not inhibit this response to prostaglandin E(1).

Acetaminophen↗
PubMed1973

The hypothermic effect of tetrodotoxin in the unanaesthetized cat.

1. The hypothermic effect on unanaesthetized cats of tetrodotoxin injected I.V. or into the lateral cerebral ventricle was examined.2. At an ambient temperature (T(a)) of 22 degrees C, tetrodotoxin given intraventricularly was over 400 times more potent in lowering body temperature (T(b)) than when given I.V. The magnitude of the hypothermia was dose-dependent for both routes. Decreases in T(b) as great as 6.8 degrees C were induced by infusions or multiple injections of tetrodotoxin into the ventricle.3. Tetrodotoxin also lowered T(b) at T(a) = 13, 30 or 35 degrees C. Tachypnoea, which lasted for longer durations and which became more intense the higher the T(a), accompanied development of hypothermia. Shivering was observed only during recovery from hypothermia at 13 degrees C.4. During the tetrodotoxin-induced hypothermia, animals were still able to regulate against environmental thermal stresses.5. EDTA disodium salt, leucocytic pyrogen and prostaglandin E(1) antagonized the hypothermic effect of tetrodotoxin when they were administered during recovery from tetrodotoxin.6. Activation of heat-loss mechanisms, and the absence of compensatory shivering during development of hypothermia after tetrodotoxin administration, plus lowering of T(b) by tetrodotoxin at T(a) above as well as below the thermoneutral temperature, indicate that lowering of the thermoregulatory set-point is the mechanism by which centrally or peripherally administered tetrodotoxin lowers T(b). Further evidence for set-point lowering after intraventricular administration of tetrodotoxin is provided by persistence of the ability to regulate against both heat and cold stresses during hypothermia. The possibility that the decrease in set-point could be due to the well known action of tetrodotoxin to block transient increases in membrane sodium ion conductance is discussed in terms of a recent hypothesis regarding ionic control of the thermoregulatory set-point.

Animals↗