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Biomedical subjects

W G Clark

Publications and source records attributed to W G Clark.

At least 73 records · Page 4Linked to original sources
PubMed1978

Comparison of the dopaminergic effects of apomorphine and (-)-N-n-propylnorapomorphine.

(-)-N-n-propylnorapomorphine (NPA) was found to be 2.3 times more active than apomorphine in producing stereotypy in novice mice. This potency ratio was not changed by reserpine pretreatment (4 h prior). However, when mice pretreated with reserpine 24 h earlier were used, NPA was found to be 6.5 times more active in producing locomotor stimulation and 8.7 times more active in producing stereotypy than apomorphine. In these mice, a second dose of reserpine or alpha-methyl-p-tyrosine (alphaMT) given 4 h prior to NPA administration considerably reduced the locomotor effects of NPA. Such treatments did not modify the effects of apomorphine. Phenoxybenzamine failed to alter the responses of both these drugs. It was concluded that, while apomorphine possesses direct dopamine (DA) receptor stimulant effect, that of NPA is partly direct and partly indirect in nature. In novice mice, NPA was 91 times more active than apomorphine in inhibiting the alphaMT-induced depletion of brain DA. The question is raised why the powerful DA receptor agonistic effect of NPA did not produce equivalent behavioral responses in mice. The likely explanation would be that, in addition to its effect on the striatonigral DA system from which the stereotypic response originates, NPA also exerts a predominant effect on the mesolimbic areas. The combined effect of NPA on these two components of the DA system is reflected in the biochemical results. The overall dopaminergic effect of NPA is several times greater than that of apomorphine.

Animals↗
PubMed1978

Naloxone does not antagonize leukocytic pyrogen.

In a crossover experiment, cats were given third cerebral ventricular injections of 500 microgram naloxone hydrochloride or saline vehicle followed in 15 min by i.v. injections of saline solution or leukocytic pyrogen. The pyrogen produced comparable fevers after both saline and naloxone pretreatment. Intravenous administration of naloxone hydrochloride (5 mg/kg) likewise did not prevent febrile responses to leukocytic pyrogen. These results indicate that endogenous opioid peptides are not likely central mediators of pyrogen-induced fevers.

Animals↗
PubMed1978

Hyperthermic responses to central and peripheral injections of morphine sulphate in the cat.

1 The effect of morphine on body temperature was studied in conscious, unrestrained cats provided with implanted third or lateral cerebral ventricular cannulae, jugular venous catheters and retroperitoneal thermocouples.2 Intraventricular injections of 2.5-50 mug and intravenous injections of 1-10 mg/kg morphine sulphate produced dose-related hyperthermic responses. Similar mean increases in body temperature after administration of a given dose were elicited in cats which had not previously received morphine and, provided that tolerance was avoided by spacing injections at least 72 h apart, in cats which received a series of injections of morphine. Morphine was at least 850 times more potent when injected into the third ventricle than when given intravenously. Increasing the dose of morphine sulphate injected into the third ventricle to 1250 mug only prolonged the hyperthermia. Morphine did not produce hypothermia at any dose tested.3 Injection of 10 mug morphine sulphate into the third ventricle produced similar hyperthermias at ambient temperatures (tas) of 4-6, 21-23 and 33-36 degrees C. The increase in body temperature was associated with shivering at the lower tas. At the highest ta, shivering was not evoked, but respiratory rate decreased after morphine if it was initially elevated. These results suggest that morphine increased the level at which body temperature was regulated.4 Neither metiamide nor indomethacin antagonized morphine so histamine and prostaglandins were apparently not required for the hyperthermic effect.

Animals↗
PubMed1978

The antipyretic effect of tilorone hydrochloride in the cat.

1 The antipyretic activity of tilorone hydrochloride was studied in conscious, unrestrained cats provided with implanted jugular venous catheters, third cerebral ventricular (i.c.v.) cannulae and retroperitoneal thermocouples. 2 In afebrile animals, 10 mg/kg i.v. or 1 mg i.c.v. tilorone hydrochloride did not alter body temperature, but 20 mg/kg i.v. or 2 to 5 mg i.c.v. caused hypothermia and various behavioural responses. 3 Non-hypothermogenic doses of tilorone (i.v. or i.c.v.) antagonized hyperthermic responses to leucocytic pyrogen (i.v. or i.c.v.), bacterial pyrogen (i.c.v.) and sodium arachidonate (i.c.v.) but did not antagonize prostaglandin E1 (i.c.v.). 4 These results indicate that tilorone has an antipyretic action within the central nervous system that is distinct from its hypothermogenic action. Although there is no published evidence to indicate that tilorone can inhibit prostaglandin synthesis peripherally, its ability to reduce hyperthermic responses to arachidonate suggests that it can inhibit prostaglandin synthesis within the brain.

Animals↗
PubMed1978

Differential effects on temperature of chlorpromazine injected into PO/AH and medulla oblongata of the rat.

Hyperthermic responses developed after injections of chlorpromazine into the preoptic/anterior hypothalamic (PO/AH) region of unrestrained rats. Sites near hte posterior border of the anterior hypothalamus were the most sensitive. Injections of chlorpromazine into the medulla oblongata did not alter rectal temperature in intact rats but caused hypothermic responses when the PO/AH region had been destroyed. These results provide additional evidence for a secondary temperature control in the medulla which ordinarily responds minimally to drugs and which may be suppressed by an intact primary control in the PO/AH region.

Animals↗
PubMed1976

Antagonism by antipyretics of the hyperthermic effect of a prostaglandin precursor, sodium arachidonate, in the cat.

1. Injection of sodium arachidonate (100-400 mug) into lateral cerebral ventricles of unanaesthetized cats caused shivering and rapid development of dose-related hyperthermic responses. Unless arachidonate is hyperthermogenic per se, this indicates that in vivo formation of prostaglandins, or perhaps an endoperoxide intermediate, can cause hyperthermia. 2. Tolerance gradually developed when arachidonate was administered repeatedly at intervals of 1-7 days. Examination of the brains of several tolerant animals revealed in each case marked enlargement of the lateral ventricles which apparently accounted for the diminished response to arachidonate. 3. Sodium salicylate (40, 160 mg/kg, i.v.) antagonized arachidonate but only after a 3-4 hr latent period. 4. Paracetamol (10, 40 mg/kg, i.v.) reduced the hyperthermic effect of arachidonate but a dose of 40 mg/kg antagonized centrally administered bacterial endotoxin more effectively than it did arachidonate. 5. Indomethacin (40 mug/kg, i.v.) significantly reduced arachidonate-induced hyperthermia in only one of two studies. This reduction was comparable to the hypothermic effect of indomethacin in afebrile animals and was attributed to a non-specific action on thermoregulatory function rather than to inhibition of prostaglandin synthesis. Indomethacin antagonized endotoxin and leucocytic pyrogen to a greater degree than it did arachidonate. 6. Comparison of the relative effectiveness of the antipyretics in blocking hyperthermic responses to pyrogens and to sodium arachidonate indicates that, if prostaglandins do mediate pyrogen-induced fever, these antipyretics exert their primary at a step before prostaglandin synthesis.

Acetaminophen↗
PubMed1976

Biphasic changes in body temperature produced by intracerebroventricular injections of histamine in the cat.

1. Intracerebroventricular administration of histamine to cats caused hypothermia followed by a rise in body temperature. 2-Methylhistamine caused a similar biphasic response, while 3-methylhistamine had no effect on body temperature and 4-methylhistamine produced a delayed hyperthermia. Some tolerance to the hypothermic activity developed when a series of closely spaced injections of histamine was given. 2. Doses of histamine and 2-methylhistamine which altered body temperature when given centrally were ineffective when infused or injected I.V. 3. Pyrilamine, an H1-receptor antagonist, prevented the hypothermic response to histamine. 4. Hypothermic responses to histamine at an environmental temperature of 22 degrees C were comparable to responses in a cold room at 4 degrees C in both resting animals and animals acting to depress a lever to escape an external heat load. A change in error signal from the thermostat could account for these results. However, lesser degrees of hypothermia developed when histamine was given to animals in a hot environment. In some, but not all animals, this smaller response could be attributed to inadequate heat loss in spite of maximal activation of heat-loss mechanisms. 5. The hyperthermic response to histamine was antagonized by central, but not peripheral, injection of metiamide, an H2-receptor antagonist. 6. The results indicate that histamine and related agents can act centrally to cause both hypothermia, mediated by H1-receptors, and hyperthermia, mediated by H2-receptors.

Animals↗
PubMed1975

Effects of prostaglandin antagonist SC-19220 on body temperature and on hyperthermic responses to prostaglandin E-1 and leukocytic pyrogen in the cat.

Intravenous injection of SC-19220 (3-9 mg/kg) caused dose-related hypothermic responses in cats. Repeated administration of SC-19220 resulted in tolerance to its hypothermic action. During SC-19220-induced hypothermia, the hyperthermic activity of both prostaglandin E-1 and leukocytic pyrogen was reduced or abolished. Neither prostaglandin E-1 nor leukocytic pyrogen was antagonized when given shortly after recovery from SC-19220-induced hypothermia or by doses of SC-19220 which did not cause hypothermia. Although these results may indicate a role of prostaglandins in normal physiological thermoregulation, it is also possible that production of hypothermia by SC-19220 is unrelated to prostaglandin antagonism.

Animals↗