摘要:

Abstract:A number of general anaesthetics and organic solvents were tested for their ability to inhibit the binding of3H‐clonidine to α2‐adrenoceptors in mouse cerebral cortex membranes. The order of potency of the tested agents was: chloroform>halothane>trichloroethylene>carbon tetrachloride>dichloromethane. Of these agents halothane was tested further. When saturation curves of3H‐clonidine were constructed, halothane (25 mmol/l added directly to the assay) was found to induce a proportionally greater inhibition at low3H‐clonidine concentrations than at high. Computer modelling these saturation curves indicated that halothane reduced the apparent affinity of3H‐clonidine; Kd= 4.2 nmol/l in the absence of halothane and Kd= 6.0 nmol/l in its presence Gassing the cortex membranes with 3% halothane induced a practically identical reduction in the affinity for3H‐clonidine; Kd= 4.6 nmol/l for the control versus Kd= 10.7 nmol/l for halothane. The effects of halothane was compared to that of the non‐hydrolyzable GTP analog Gpp(NH)p. Gpp(NH)p in the concentration range 10‐8‐10‐3mol/l dose‐dependently reduced the binding of 1 nmol/l3H‐clonidine, the effect being essentially maximal at 10‐4mol/l. Computer modelling of saturation curves of3H‐clonidine indicated that 0.1 mmol/l Gpp(NH)p reduced the apparent affinity of 3H‐clonidine; Kd= 5.4 nmol/l in the absence of Gpp(NH)p and Kd= 9.3 nmol/l in its presence. In addition Gpp(NH)p caused some reduction in the apparent number of3H‐clonidine binding sites. The effect of halothane on3H‐clonidine binding was tested both in the absence and presence of 0.1 mmol/l Gpp(NH)p. During these conditions halothane was slightly more potent in the presence of Gpp(NH)p (IC50 of halothane = 17 mmol/l) than in its absence (IC50 = 41 mmol/l). The data suggest that halothane induces a direct conformational change in the ligand binding subunit of the α2‐adrenoceptor that decreases its affinity for3H‐clonidine. The results are discussed with respect to possible mecha

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1987.tb01817.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Abstract:The effects of 25 mg propiomazine were examined in ten healthy volunteers in a sleep laboratory setting. A significant decrease in sleep latency and a corresponding decrement in subjectively assessed sleep latency was found during drug treatment. The distribution of the different sleep stages was affected to a relatively small extent. Some evidence for a suppression of REM‐sleep in the early part of the treatment period was found. Based on subjective assessment, the subjects rated their sleep quality as significantly improved during treatment. Ratings of “drowsiness in the morning” were not different during baseline and drug treatment, but there was a significant decrease at withd

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1987.tb01818.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Abstract:3H‐Alaproclate, a selective 5‐hydroxytryptamine uptake inhibitor, was found to bind to microsomal membranes from the rat liver with high affinity (KD= 3 nM) and large capacity (Bmaxabout 2 nmol/g liver). This binding was stereoselective since S‐(‐)‐alaproclate was 30 times more potent than the R‐(+)‐enantiomer to displace the3H‐labelled racemate. Proadifen (SKF 525A), an inhibitor of cytochrome P‐450, displaced the3H‐alaproclate binding with the same, high affinity (Ki= 3 nM) as alaproclate itself. Repeated treatment with phenobarbital sodium (5 × 75 mg/kg intraperitoneally) increased the number of alaproclate binding sites 7–8 times without changing the affinity. However, most of the phenobarbital induced3H‐alaproclate binding was not displaceable by proadifen, showing the presence of at least two different high affinity binding sites. The possible involvement of cytochrome P‐450 in the alapro

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1987.tb01819.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Abstract:The binding of3H‐alaproclate, a selective 5‐hydroxytryptamine uptake inhibitor, to membranes prepared from the rat cerebral cortex was investigated by a filtration technique. It was found that3H‐alaproclate bound with high affinity to three or four different sites and to one low affinity site. The binding to two of these sites was displaceable by 1 μM proadifen (SKF 525A), an inhibitor of drug metabolism. From iterative nonlinear regression analysis the KD‐values of these sites were calculated to about 1 and 28 nM and the Bmaxvalues 1.5 and 19 pmol/g wet tissue, respectively. The high affinity binding that was not displaceable by proadifen but by 10 μM alaproclate had KD‐values of 1 nM and 6 nM and Bmax‐values of 0.4 and 2 pmol/g wet tissue. The low affinity binding that was not displaceable by proadifen had a KD‐value of about 200 nM and a Bmax‐value of about 90 pmol/g tissue. The possible relationship between the proadifen sensitive high affinity binding of3H‐alaproclate and the brain cytochrome

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1987.tb01820.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Abstract:Electrophysiologic and circulatory effects of a single oral dose of verapamil (120 mg) were evaluated in 8 patients with symptomatic sick sinus syndrome. Ninety min. after verapamil, calcium gluconate (1375 mg) was infused in an attempt to reverse the depressor actions of the drug. Verapamil significantly increased sinus node recovery time (P<0.05) and atrioventricular conduction time (P<0.01), and decreased both systolic (P<0.01) and diastolic blood pressure (P<0.05) and spontaneous heart rate (P<0.01). Intravenous calcium significantly reversed blood pressure reduction (P<0.001) and further lowered heart rate (P<0.05) without affecting sinus node recovery time and atrioventricular conduction significantly. There was no significant correlation between plasma verapamil concentrations and any of the cardiovascular parameters. These data confirm that verapamil is principly contraindicated in patients with sinus node dysfunction and demonstrate that the actual calcium dose, although partly reversing blood pressure reduction, cannot reverse the depressant action of the drug on the sinus and atrioventricular node in such patients.

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1987.tb01821.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Abstract:Three healthy male volunteers were given a codeine (1 mg/kg) solution in the absence and presence of ethanol in a cross‐over designed study. The blood ethanol concentration was kept at approximately 16 mM for 8 hrs. Blood samples were taken at several occasions during the first day after the codeine administration. Urine was sampled during three days. There were no significant differences in the area under serum concentration versus time curve in the absence and presence of ethanol with respect to free codeine, total codeine and total morphine. The fraction of codeine glucuronized in serum (approximately 94%), the maximum serum concentration of free (0.34 μM) and total codeine (6.3 μM), the time to reach the maximum serum concentration values (approximately 65 min.) were also similar in the absence and presence of ethanol. The accumulated percentage of the codeine dose given which was found as codeine and morphine and their conjugates in the urine ranged from 50 to 91 percent in the different subjects. The accumulated percentage of the administered codeine dose found as free morphine in the urine, was significantly lower in the ethanol exposed individuals (0.18$pL0.03%) compared to the controls (0.39$pL0.09%). The percentage of the codeine dose found in the urine in the control situation as free codeine (5.2$pL2.2%) was not statistically different from the amount found in the urine after ethanol treatment (4.3$pL2.0%). The percentage glucuronized morphine (95.3$pL0.4%) and codeine (91.9$pL2.2%) in the urine in the absence of ethanol was similar to glucuronized morphine (95.3$pL2%) and codeine (93.1$pL3%) after ethanol exposure. The results suggest that there is probably no significant biological interaction of ethanol with codeine pharmacokineticsin vivoin hum

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1987.tb01822.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Abstract:The effects of two partial agonist opioid analgesics, meptazinol (at doses 0.7 and 1.4 mg/kg intravenously) and pentazocine (at doses 0.3 and 0.6 mg/kg), on anterior and posterior pituitary hormone secretion were studied in six normal human volunteers. Both drugs stimulated the secretion of prolactin dose‐dependently, as expected. This effect was seen in all subjects, although two of the six subjects reacted more sensitively to both drugs. Plasma growth hormone concentrations were increased only after the higher dose of meptazinol. This was also seen in all subjects suggesting a spesific pharmacological effect. Vasopression (AVP) in plasma was greatly increased (up to 76 pg/ml) in three of the six subjects after the higher dose of meptazinol, but remained on a low level in the other three and after all other drug doses. The increase in AVP occurred only in those individuals who reported nausea after meptazinol. It was concluded that the augmented AVP release following meptazinol administration was likely to be a non‐specific response induced by nausea and not an effect mediated by opiate recept

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1987.tb01823.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Abstract:Rats were exposed to toluene, 500 p.p.m., for 12 hrs/day for up to 80 weeks. The brains were removed and the synaptosomes were prepared. Potassium‐stimulated and unstimulated synaptosomes were incubated with45Ca2+for 1/2, 2, 4, 8, and 16 min. Toluene exposure for 4 and 12 weeks caused a significant, approximately 20%, increase in45Ca2+uptake into unstimulated synaptosomes. The effect was of moderate quantity and transient, since it was not significant after 30 and 80 weeks of exposure. It seems doubtful whether the demonstrated change in calcium uptake should have any relevance in connection with the “organic solvent neurotoxicity syndro

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1987.tb01824.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Abstract:Sleeping time was measured in groups of old and young rats following the intraperitoneal injection of pentobarbital (39.5 mg·kg‐1), diazepam (30 mg·kg‐1) and ethanol (3 g·kg‐1). Concentrations of pentobarbital, and unbound and total diazepam in serum, and ethanol in breath were quantified; as well as whole brain concentrations of diazepam and N‐demethyldiazepam. Healthy old rats slept significantly longer than young rats after receiving diazepam and ethanol but not pentobarbital. There were no significant differences in serum or whole brain concentrations of diazepam or N‐demethyldiazepam between healthy young and old rats. There were also no changes in the serum pentobarbital or breath ethanol concentrations between the young and old rats. Increases in pharmacologic effect that occur with aging may be caused by alterations in pharmacokinetic parameters or changes at the site of drug action. The cause of an increased pharmacodynamic effect depends upon the specific drug, possibly because these compounds affect the same receptorionophore complex at dif

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1987.tb01825.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Abstract:Sensitivity to fluoride of human gingival fibroblasts derived from six different normal tissues (donor age; 17–36 years, male and female) and a foetal tissue were studied by measuring cell growth and protein synthesisin vitro.Fibroblasts derived from four different human foetal lungs were also studied in order to compare them with the gingival cells. Two cell lines of gingival and lung fibroblasts were derived from the same foetus. All of the young adult and adult gingival cells grew slowly in the medium containing 1.32 mM fluoride, while foetal cell growth, including the foetal gingival cells, was completely inhibited. Both foetal cultures had faster cell replication rates and greater protein synthesis rates than those of the young adult or adult cultures. The fluoride sensitivity was lower in all young adult and adult gingival fibroblasts than in the foetal cells. However, “aged” foetal cultures obtained by serial passage showed lower fluoride sensitivity. These “aged” cells also had prolonged generation times. These findings indicate that although the mechanism is unclear, the low fluoride sensitivity of the young adult and adult gingival fibroblasts observed in this study are likely to be related to their slower rate of ce

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1987.tb01826.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY