Inhibition of pyrogen Escherichia coli fever with intracerebral administration of prazosin, dihydrobenzperidol and nifedipin in the rabbits.

1. The thermoregulatory, effector processes were investigated after treatment with prazosin (PRA), dihydrobenzperidol (DHBP) and nifedipin (ADA) applied to the thermosensitive zone of the anterior hypothalamus (PO/AH) on normothermic and feverish rabbits (LPS, lipopolysaccharide E. coli; 1 meg/kg, i.v.). 2. The alpha 1-noradrenergic receptor antagonists, PRA and DHBP, applied to the PO/AH produced an abolishment of fever elicited by pyrogen i.v. injection mainly because of vasodilation of ear skin vessels and attenuation of metabolic rate. 3. Calcium channel blocker, ADA, also induced a decline in the rabbit's core temperature in the same manner. 4. All these drugs given to the PO/AH did not change the body temperature in normothermic rabbits. 5. These results, therefore, strongly suggest that alpha 1-noradrenergic receptors subserve the coordinated thermoregulatory mechanisms in PO/AH which are required for antipyresis. The inhibition of Ca2+ turnover is discussed as a possible mechanism of antipyretic action of these drugs given to the PO/AH.

The pharmacologic activity of complexes and mixtures with copper and salicylates or aminopyrine following oral dosing in rats.

Cu(II) complexes with salicylates or aminopyrine were administered to rats with local inflammation (acute paw oedema elicited with carrageenan) to determine their anti-inflammatory activity and ulcerogenic effects following oral administration. The complexes were more effective than the parent ligands or appropriate mixtures of these ligands with Cu(II) as anti-inflammatory agents. All complexes indicated low ulcerogenity. The differences in pharmacologic activity between the complexes and mixtures in question are discussed.

Effects of prazosin on metabolism and body temperature in normothermic rabbits.

An attempt was made to study the influence of prazosin on thermoregulatory parameters. Two sets of experiments were carried out in rabbits. In the first set of experiments prazosin was given as 3 h infusion intravenously, (iv) (0.1, 0.25 and 0.5 mg/kg/h) or intracerebroventricularly, (icv) (20, 50 and 100 micrograms/animal) at an ambient temperature of 22 degrees C. Iv infusion caused a fall while icv administration a rise in body temperature. In the second set of experiments at different ambient temperatures (Ta = 4, 22, 28 degrees C) the following thermoregulatory parameters were recorded: rectal (Tre) and ear skin (Te) temperatures, metabolic rate (M), respiratory heat loss (Eres). The most evident result of iv infusion of prazosin in a dose of 0.25 mg/kg/h was a fall in Tre accompanied by a decrease in metabolic rate at ambient temperature of 4 degrees C. At Ta of 22 degrees C and 28 degrees C prazosin iv (0.25 mg/kg/h) induced only minimal changes in measured parameters. The results of the experiments may suggest that prazosin given peripherally induced hypothermia at Ta of 4 degrees C by inhibition of non-shivering thermogenesis.

Effect of ascorbic acid in the presence of neomycin on isolated rat stomach strips.

The effects of vitamin C and acetylcholine on the smooth muscle of rat stomach were compared after neomycin-induced blockade of phosphatidylinositol metabolism. The cumulative curves of dose-dependent responses showed a non-competitive antagonism between vitamin C and neomycin. On the other hand, the antagonism between acetylcholine and neomycin was of a mixed, competitive-non-competitive type. The results of the experiments suggest the conclusion that a normal metabolism of phosphatidylinositol controlling calcium transport into the cells is necessary for the stimulating effect of vitamin C on the contractions of the smooth muscles in the digestive tract.

Ascorbic acid, PGE2 and acetylcholine interaction: the effect on isolated smooth muscle.

The action of L-ascorbic acid (AA) on the isolated rat stomach fundus and guinea pig ileum was studied. AA induced contractions of these organs and potentiated the effect of ACh and PGE2. The contractile effect of AA was potentiated by eserine and inhibited by atropine. Dose-response relations suggest a stimulatory effect of AA on the muscarinic receptor.

Differences between the effect of prazosin and lysine-acetylsalicylate on some thermoregulatory parameters in nonfeverish rabbits.

Thermoregulatory responses to prazosin and lysine-acetylsalicylate (LAS) were investigated in afebrile rabbits at different ambient temperatures, i.e. at 5, 21 and 28 degrees C. In cold as well as in heat prazosin significantly inhibited the metabolic rate. This effect was accompanied by falls in rectal temperatures, particularly at the ambient temperature of 5 degrees C. Increases in ear skin temperatures became visible only when this drug was used in rabbits maintained in the thermoneutral environment. On the other hand LAS in all tested conditions indicated a marked metabolic activity associated with an intensified respiratory heat loss. As a consequence, the rabbits responded with slight increases in body temperature. The possible mode of thermoregulatory activity of prazosin is being considered in confrontation with that of LAS.

The influence of dopamine on active sodium transport across frog skin measured as short circuit current.

The influence of dopamine (DA) on short circuit current (SCC) across isolated Rana esculenta skin was studied to determine whethera a DA receptor system exists in that cell membrane model and what is the influence of DA on SCC. Experiments were carried out with both alpha- and beta-adrenergic blockers and cocaine present in the Ringer solution. DA in cumulative doses added to the inner Ringer solution stimulated SCC in a dose-dependent manner. Apomorphine (10(-5) M) shifted the DA dose--response curve to the left and increased the maximum DA response. Haloperidol (10(-9) M) antagonized the effects of the DA depressing maximum response as well. Imidazole (10(-8) M and 10(-9) M) antagonized the influence of DA in a manner similar to haloperidol. It appeared that there were DA receptors in frog skin and that haloperidol as well as imidazole were DA antagonists which acted non-competitively.