ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1977.tb03210.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

摘要:

AbstractEffects of two pure chlorobiphenyls (2,4′,5‐trichlorobiphenyl or 2,2′,4,4′,5,5′‐hexachlorobiphenyl) on the hepatic drug metabolizing system and on the elimination rate of14C from the blood after intravenous injection of 4‐14C‐ progesterone have been studied in the female rat. The results obtained show that females pre‐treated with small amounts of 2,2′,4,4′,5,5′‐hexachlorobiphenyl (0.5 mg/day for 14 consecutive days) have significantly higher elimination rates of14C (originating from intravenous injection of 4‐14C‐progesterone) from the blood plasma, significantly higher content of hepatic cytochrome P‐450 and significantly heavier livers than control females. On the other hand, the results obtained from females pre‐treated with small amounts of 2,4′,5‐trichlorobiphenyl (0.5 mg/day for 14 consecutive days) do not differ significantly from the

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1977.tb02117.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

摘要:

AbstractIsoproterenol (IPR) induces damage to the heart of frogs living at 25°. The resistance of an isometric ventricular strip to histotoxic anoxia induced by cyanide is significantly reduced 4 hours after one injection of IPR and still more after repeated injections. Macroscopically visible heart lesions are observed only on the first two days after the second injection of IPR. The response of the heart muscle preparation to cyanide is then continuously improved during 3‐4 weeks after IPR and the disturbance of the myocardial function is thus only temporary and may at least partly be induced by metabolites of the catecholami

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1977.tb02118.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

摘要:

AbstractThe disposition of radioactivity was studied after administration of a new oral hypoglycaemic agent,14C‐labelled CS 476, to rats, rabbits and dogs at a pharmacologically active dose level of 0.2 mg/kg and to human subjects at a therapeutic dose level of 5 mg. After oral doses, most of the drug was excreted in the faeces by rats and dogs and faecal radioactivity was obtained from biliary excretion. Rabbits and humans excreted most of the dose in urine. Unchanged CS 476 was the major radioactive component in the plasma of all the species during 6 hours after dosing, and was extensively bound to the plasma proteins. The half‐life of CS 476 in plasma was 2 hours in dogs and humans, and 16 hours in rabbits. Drug accumulation did not occur in dog and rabbit plasma during a period of consecutive daily doses and the half‐lives after the last of the repeated doses were similar to those found after single doses. In rats, plasma concentrations were relatively low, and did not reach the peak level found in female rats until 24 hours after dosing. CS 476 was extensively bio‐transformed. The apparent species‐dependent disposition of CS 476 may explain differences in tolerance to chro

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1977.tb02119.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

摘要:

AbstractThe relative brain uptake (extraction into brain) of delta‐9‐tetrahydro‐cannabinol (delta‐9‐THC) and the primary metabolite 11‐OH‐delta‐9‐tetrahydrocannabinol (11‐OH‐delta‐9‐THC) was measured after close intracarotid injection in rats of radiolabelled moities using labelled antipyrine as reference. The extraction percentage was of the same magnitude when injections were given in saline, 66 ± 11 % and 70 ± 9 % respectively after 5 sec., 59 ± 4 and 67 ± 8 respectively after 15 sec. While the extraction of 11‐OH‐delta‐9‐THC was the same when injected into plasma, the extraction of delta‐9‐THC was only about half of the extraction from saline, and also half the extraction of the metabolite from plasma. The higher uptake quantity of the metabolite into the brain may account for the relatively greater effect on the central nervous system of the metabolite than of the parent compound at equal concentrations in plasma. Moreover our experiments demonstrate that 11‐OH‐delta‐9‐THC formed in the liver after cannabis (delta‐9‐TH

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1977.tb02120.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

摘要:

AbstractWhen the local anaesthetic drug lidocaine is added to liver microsomes biphasic type I spectral change titration curves can be observed. A high‐affinity and a low‐affinity phase is observed. In the present study we have found that microsomes from female rats have a dominant high‐affinity phase, which can hardly be observed within microsomes from female guinea pigs. Male rats showed an intermediate phase. On incubation of lidocaine at concentrations of 1 γM or less with female rat liver microsomes a larger fraction of the drug was aromatically hydroxylated than deethylated. The opposite was true for guinea pig liver microsomes, and microsomes from male rats were intermediate. The ratio between the formation of deethylated and hydroxylated metabolites increased with the lidocaine concentration and at a lidocaine concentration of 10‐4M deethylation was the dominant oxidation type in all microsomes. The data suggest that the two spectral phases represent two binding sites of cytochrome P‐450 each having a certain “catalytic specificity” ‐ the high affinity catalyzing aromatic hydroxylation and the “low‐affinity site” deethylation. This hypothesis is further supported by the observed differential effects of pH and MgCl2concentration on the

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1977.tb02121.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

摘要:

AbstractThe urinary elimination of thiocyanate was investigated in male and female rats following the chronic administration of potassium cyanide. Female rats dosed at the level of 5 mg KCN/kg once a week and twice a week respectively, displayed no significant difference in the excretion of thiocyanate in urine after periods of up to eight weeks of study. Similarly, male rats that were administered 5 mg/KCN/kg twice weekly showed no significant difference in the amount of thiocyanate excreted. The elimination patterns of thiocyanate in male and female rats showed no significant differences. The results suggest that a substrate saturation phenomenon is not operative with cyanide metabolism at the dosage level of potassium cyanide employed in this study. This is contrary to a previously published study which reported that the urinary excretion of thiocyanate decreased after chronic potassium cyanide administration.

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1977.tb02122.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

摘要:

AbstractFrom a homogenate of rabbit colon muscle two ATP dependent Ca‐accumulating microsomal fractions were isolated by differential centrifugation on a sucrose density gradient at 35 % and 35‐45 % sucrose. Adenylate cyclase and phosphodiesterase activities were found in the fractions. The Ca‐accumulation and the ATPase activity of these fractions were stimulated by cyclic AMP (10‐5M) at an ATP concentration of 0.35 mM ATP. In the presence of higher concentrations of ATP (5 mM) cyclic AMP had no effect on the Ca‐binding. The higher concentration of ATP markedly increased the cyclic AMP formation in relation to the activity found at the lower concentration of ATP. Isoprenaline (2 × 10‐6M) stimulated the Ca‐accumulation in the 35‐45 % fraction and increased the hydrolysis of ATP. These effects were absent in the fraction isolated at 35 % sucrose. In the former fraction isoprenaline also stimulated the adenylate cyclase activity at 0.35 mM but not at 5 mM ATP. Both the effect of isoprenaline on the Ca‐binding and the adenylate cyclase activity were inhibited by the adrenergic β‐receptor blocking agent sotalol. In the 35‐45 % fraction papaverine (1 × 10‐3M) stimulated the Ca‐accumulation and inhibited the phosphodiesterase activity. It is suggested that cyclic AMP and agents which influence the cyclic AMP metabolism in the microsomes may have a regulatory role on the

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1977.tb02123.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

摘要:

AbstractConcentrations of nitrazepam in plasma were determined by gas chromatography in healthy volunteers after an acute peroral administration of nitrazepam (5 and 10 mg). Placebo tablets were also used, and an assessement of subjective drug effects was made during each medication. In addition serum growth hormone levels were determined. The peak plasma nitrazepam concentration was achieved at 120 minutes (46.9 ± 3.2 ng/ml, mean ± S.E.M.) after 5 mg of nitrazepam and at 180 minutes (82.8 ± 10.5 ng/ml) after the dose of 10 mg. The half‐life of nitrazepam in plasma ranged from 16.5 to 48.3 (mean 28.8) hours. A significant positive correlation was seen between the subjective sedative effects and the magnitude of the peak nitrazepam concentrations in plasma. This drug effect was highly significant when the plasma levels of nitrazepam were rising. The subjective sedative effects were more prominent after 10 mg than after 5 mg dose of nitrazepam. The plasma nitrazepam concentration was not significantly correlated with the subjective sedative effect the next morning, 12 hours after the drug intake. Serum growth hormone levels rose significantly during the study both after 5 mg and 10 mg nitrazepam doses (peak levels 16.3 ± 4.0 and 12.7 ± 3.1 ng/ml) and were significantly higher than after placebo administration (3.7 ± 0.7

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1977.tb02124.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

摘要:

AbstractThe concentrations of nitrazepam in the plasma and cerebrospinal‐fluid (CSF) of 38 neurological patients were determined by gas chromatography 2‐36 hours after a single 5 mg oral dose. The percentage ratio between the mean CSF and the plasma concentrations increased from 8.0 % at 2 hours to 15.6 % at 36 hours. This percentage rise was significant (P<0.001). The maximum concentration of nitrazepam in the plasma was 36.7 ± 5.7 ng/ml (at 2 hours) and CSF 3.0 ± 0.3 ng/ml (at 4 hours). During the β‐phase the half‐life of nitrazepam in plasma was about 27 hours and in the CSF markedly longer about 68 hours, indicating a very slow elimination of nitrazepam fr

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1977.tb02125.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY