摘要:

Studies were undertaken to assess the ability of various in vitro and in vivo pentobarbital-metabolizing systems to reflect modifications in pentobarbital response following treatment with either phenobarbital or SKF 525-A. Of the in vitro systems studied, the hepatic 10,000 g supernatant and washed microsome fractions and liver slices reflected varying degrees of phenobarbital-induced stimulation of pentobarbital metabolism. Significant SKF 525-A-induced inhibition of pentobarbital metabolism was observed in the hepatic microsome fraction, liver slices, and isolated perfused liver. Plasma level decline of pentobarbital, however, was identified as the measure of pentobarbital metabolism which best reflects both phenobarbital- and SKF 525–A-induced modification of the duration of pentobarbital response. In correlating the in vitro systems with the in vivo systems of pentobarbital metabolism, both the hepatic 10,000 g supernatant and washed microsome fractions reflected phenobarbital-induced alteration of in vivo pentobarbital metabolism as determined by plasma level decline. None of the in vitro metabolism systems employed adequately reflected modification of the in vivo metabolism of the barbiturate following SKF 525-A treatment. These studies indicate that major differences exist in the sensitivity and responsiveness of in vitro hepatic and in vivo systems in their capacity to reflect modification of pentobarbital response and metabolism following phenobarbital and SKF 525-A treatment. Furthermore, the plasma level decline of a lipid-soluble drug provides the best index of hepatic drug metabolism which reflects modification of drug response following phenobarbital or SKF 525-A pretreatmen

ISSN:0031-7012    

DOI:10.1159/000136765

出版商:S. Karger AG    

年代:1978

数据来源: Karger

摘要:

Sodium salicylamide in doses of 650 and 1,300 mg was evaluated in two separate sleep laboratory drug evaluation studies of insomniac patients. Each study utilized a standard protocol of 10 consecutive laboratory nights consisting of four placebo nights for adaptation and baseline, three drug nights for short-term drug administration and three placebo nights for evaluating withdrawal. Neither dose had a clear-cut hypnotic effect in inducing or maintaining sleep. Sleep stages were not affected by drug administration or drug withdrawal. Both the objective findings and subjective estimates suggest that the 1,300-mg dose may have a slight sedative effect. However, when salicylamide is used as an ingredient in over-the-counter preparations, the usual dose is only 200–400 m

ISSN:0031-7012    

DOI:10.1159/000136766

出版商:S. Karger AG    

年代:1978

数据来源: Karger

摘要:

Lever-pressing rates plotted as a function of number of hours of food deprivation produces an inverted U curve, the activation performance curve. Since Δ9-tetrahydrocannabinol depresses the response rate on variable interval (VI) performance, it may be that the response depression reflects changes in this curve. Rats were tested on VI performance at five levels of food deprivation and were treated with a vehicle control, marijuana extract distillate (MED) at 7.5 and 11.25 mg/kg, cannabidiol (CBD), at 15 mg/kg or combinations: 7.5 mg/kg MED + 15 mg/kg CBD and 11.25 mg/kg MED + 15 mg/kg CBD. MED produced a depression of VI performance which was greatest at low levels of deprivation. CBD did not depress performance. When CBD was combined with MED, potentiation of depression occurred. The potentiation depression was not additive, but occurred at high levels of deprivation. It appears that MED depresses performance most at low levels of deprivation and that CBD potentiates the depression produced by MED at high levels of deprivation

ISSN:0031-7012    

DOI:10.1159/000136767

出版商:S. Karger AG    

年代:1978

数据来源: Karger

摘要:

The disposition of 4’-(9-acridinylamino)-methanesulfon-m-anisidide (AMSA), a new antitumor agent presently undergoing clinical evaluation, was studied in mice and rats following oral administration and compared to that observed following intravenous administration. The metabolic fate of AMSA was the same with either intravenous or oral administration; however, the tissue distribution of AMSA differed significantly between the two routes of administration. Following absorption from the GI tract, AMSA was rapidly cleared from plasma by the liver and excreted in the bile as metabolites. Concentrations of AMSA in the liver were relatively high after oral administration and were sufficient to exert a cytotoxic effect on LI210 cells implanted at the site. The results indicate the use of AMSA orally to attain selective localization in the liver with decreased systemic exposure, which may prove useful against tumor metastases to the liver or primary hepatocellular carcinom

ISSN:0031-7012    

DOI:10.1159/000136768

出版商:S. Karger AG    

年代:1978

数据来源: Karger

摘要:

Bilateral stopping of plantar perspiration in the mouse was obtained by application of a cotton-wool swab soaked in a 3% solution of BRL 556 in 60% ethanol for 1–2 min to the plantar surface of its right hind paw. For humans, aerosols which are at present on the market produce a sensible reduction in palmar sweating. The effect was recorded and illustrated by a modified hygrophotographic technique in which the sweat, released in the form of water vapor, was recorded by the hygrophotographic film, without any contact with the skin. In the mouse, the recording was carried out by the application to the plantar surface of a piece of hygrophotographic film, by the aid of an adhesive tap

ISSN:0031-7012    

DOI:10.1159/000136769

出版商:S. Karger AG    

年代:1978

数据来源: Karger

摘要:

Pregnenolone-16α-carbonitrile (PCN), administered twice daily p.o. for 3 days at a dose level of 20 μmol/100 g body weight, significantly enhances the in vivo binding of 14C-bilirubin and sulfobromophthalein (BSP) to hepatic Y and Z proteins in female Charles River CD® rats. 14C-bilirubin-binding to Y protein showed a 61% increase, while binding of the same moiety to the Z protein fraction was augmented by 59%. BSP-binding in vivo demonstrated rises of 114 and 71% in relation to Y and Z proteins, respectively. These data correlate well with previous investigations in which PCN was found to have a beneficial influence on experimentally induced hyperbilirubinemias and, furthermore, there is an indication that phenobarbital, another potent microsomal enzyme inducer, acts via a similar mechani

ISSN:0031-7012    

DOI:10.1159/000136770

出版商:S. Karger AG    

年代:1978

数据来源: Karger

摘要:

The acridine derivative 4’-(9-acridinylamino)-methanesulfon-m-anisidide (AMSA, NSC-141549), a new antitumor agent undergoing phase I clinical evaluation, is highly active against B16 melanoma in vivo. AMSA was found to be concentrated in B16 melanoma cells in vivo and remained at high concentrations for at least 72 h. Subcellular fractionation of B16 melanoma cells revealed the drug to be bound to melanin granules. The results suggest the possible use of AMSA in human melanoma and the design of other antimelanoma agents that would exploit the affinity of the acridine nucleus for melani

ISSN:0031-7012    

DOI:10.1159/000136771

出版商:S. Karger AG    

年代:1978

数据来源: Karger

摘要:

The effects of d-amphetamine on several measures of activity and spontaneous alternation were evaluated in rats chronically exposed to a low level of lead acetate via maternal milk during the neonatal period. Alterations in the amphetamine responses of lead-treated rats were observed with some measures of activity and exploration but not with others. ‘Paradoxical’ responses were observed with postural rearing and spontaneous alternation. No drug response was seen in lead-treated animals with respect to center field activity in contrast to a large increase seen in controls. Normally, amphetamine reduces grooming behavior, but since this reduction was greater in lead-reared than in control rats, the data suggest that for this measure the lead-reared rat may possess an increased sensitivity to amphetamines. These results were discussed in terms of the behavioral parallels found between lead poisoning and childhood hyperactivity, and the potential of this model as an animal analog of minimal brain dysfunction hyperactiv

ISSN:0031-7012    

DOI:10.1159/000136772

出版商:S. Karger AG    

年代:1978

数据来源: Karger

ISSN:0031-7012    

DOI:10.1159/000136773

出版商:S. Karger AG    

年代:1978

数据来源: Karger

ISSN:0031-7012    

DOI:10.1159/000136774

出版商:S. Karger AG    

年代:1978

数据来源: Karger