摘要:

AbstractThe pharmacokinetics of dihydroergotamine (DHE) was studied in 6 beagles after a single 2.0 mg intravenous dose and after a continuous intravenous infusion (dose 2.0 mg, infusion time 51 min. = 2.8–3.5 μg/min./kg). The concentrations of DHE in the plasma during 6 hours were determined by a radioimmunoassay. The mean α‐phase T1/2 was 0.92 min. and 5.93 min., the mean β‐phase T1/2 was 104.42 min. and 115.79 min., and the mean plasma clearance value 202.88 ml/min. and 234.79 ml/min. after a single intravenous injection and a continuous infusion administration, respectively. Similarly, the Vdc— values were 0.12 l/kg and 0.38 l/kg and the Vdβ— values 3.41 l/kg and 4.31 l/kg. Only the α‐phase T1/2and the Vdc‐values differed significantly from each other. The simulated concentrations of DHE in the peripheral compartment increased rapidly explaining its fast effect on the vasculatu

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1980.tb02448.x

出版商:Blackwell Publishing Ltd    

年代:1980

数据来源: WILEY

摘要:

AbstractThe concentrations of methylergometrine (M) (methylergonovine) in the plasma, uterus, liver, and kidneys of the rabbit were determined by a radioimmunoassay after a single 0.2 mg/kg intravenous injection and the drug responce was studied in the uterusin situ. M disappeared quickly from the plasma with a mean distribution phase half‐life of 0.91 min. According to the fast uterine tissue uptake of M the drug response in this effector organ began quickly. The simulated concentrations in the peripheral compartment of the two‐compartment open model can be useful in the understanding of the rapid drug effect, but they do not describe the real situation in any particular tis

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1980.tb02449.x

出版商:Blackwell Publishing Ltd    

年代:1980

数据来源: WILEY

摘要:

AbstractTen clinically normal male beagle dogs were used in the study. Two dogs served as control, 4 received 2 mg lead/kg daily and 4 received 5 mg lead/kg/daily. Lead was administered for 13 weeks, after which one‐half of each experimental group was treated with calcium ethylene diaminetetraacetate (CaEDTA) for 5 days. All animals were then monitored for another 4 weeks. Blood lead levels, haematology, blood glutathione concentration, and the number of bone marrow cells with stainable iron granules were measured weekly during the 18‐week experimental period. Clinical signs of poisoning were observed only in one dog in the high dose group after 6 weeks. The signs included emaciation, anorexia, muscular weakness, evidence of abdominal pain and depression. These signs were reversed with cessation of lead dosing and CaEDTA treatment. Blood lead levels and the number of marrow cells with non‐haeme iron increased in both lead‐dosed groups; nucleated red blood cells increased only in high lead dosed group. There was a trend for an increased packed cell volume in all groups; however, the high lead dosed group did not increase as fast. No significant changes were observed in blood glutathione concentration and in other haematologic parameters. There were no differences in the parameters studied between the dogs treated with CaEDTA and those not so treated. Blood lead levels and the number of nucleated red blood cells decreased after cessation of lead administration and the number of marrow cells with iron also tended to decrease after lead

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1980.tb02450.x

出版商:Blackwell Publishing Ltd    

年代:1980

数据来源: WILEY

摘要:

AbstractThe bioavailability of orally administered L‐5‐hydroxytryptophan in steady state was investigated at four increasing multiple dose levels in five patients suffering from various myoclonic disorders. An L‐aromatic amino acid decarboxylase inhibitor was co‐administered in all the experiments. The disposition pharmacokinetics of the amino acid had been established in the same patients in preceding intravenous single dose experiments. The finding of a direct proportionality between the size of the oral dose level of L‐5‐hydroxytryptophan and the corresponding areas under the plasma concentration curves within a dosage interval at steady state strongly indicates dose independent, linear pharmacokinetics of the compound. The systemic availability of L‐5‐hydroxytryptophan exhibited an interindividual range of 47–84%, with a mean value of 69.2% ±4.7 S.E.M. The absorption took place at a rather slow rate as judged from times of 1.8 to 3.3 hours elapsing from administration of the compound until occurance of the maximum measured plasma concentrations. Transitory nausea and vomiting were only recognized in few instances during the gradual building up of increasing steady state levels of L‐5‐hydroxytryptophan in the patients, and the importance of a slow initiation of therapeutical treatment with the am

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1980.tb02451.x

出版商:Blackwell Publishing Ltd    

年代:1980

数据来源: WILEY

摘要:

AbstractThe cardiac effects of supratherapeutic concentrations of two tricyclic antidepressants were studied in isolated rabbit hearts, which were perfused with a modified Krebs‐Henseleit solution containing 0.25 or 0.50 μg ml‐1of amitriptyline or 0.28μg ml‐1of clomipramine. The followingparameters were continuously recorded: heart rate, amplitude and rate of contraction, coronary flow rate, myocardial oxygen consumption and ECG. The lowest concentration of amitriptyline caused a time correlated decrease (20%) in the frequency of spontaneous beating and a pronounced decrease in the amplitude (62%) and rate of cardiac contraction (58%). Maximum increases of the PQ‐interval of about 46% and of the QRS‐complex of about 100% were observed. At the higher amitriptyline concentration these effects further increased. Clomipramine 0.28 μg ml‐1also had a very pronounced and time correlated negative inotropic effect, but the effects upon the conduction velocities were substantially lesser than those produced by the equimolar concentration of amitriptyline. The compounds caused only insignificant changes in coronary flow. The oxygen consumption did not decrease in proportion to the decrease in contractility, as an expression of decreased myocardial efficiency. The effects of the drugs are discussed in relation to their myocardial accumulation pharmacokinetics and influence upon the membraneous sodium and calcium flux and intracellu

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1980.tb02452.x

出版商:Blackwell Publishing Ltd    

年代:1980

数据来源: WILEY

摘要:

AbstractExperiments were performed to examine whether non‐hydroxylated tryptamines and 4‐chloroamphetamine utilize the membrane 5‐hydroxytryptamine carrier to pass into serotoninergic neurones. The accumulation and deamination of14C‐tryptamine by mouse brain slices or homogenates of rat hypothalamus were not inhibited by cocaine or norzimelidine, a selective inhibitor of the neuronal 5‐HT uptake. The prevention by α‐methyltryptamine (10 mg/kg, intraperitoneally), α‐ethyltryptamine (20 mg/kg intraperitoneally) and 4‐chloroamphetamine (20 mg/kg intraperitoneally) of the irreversible inhibition of monoamine oxidase by pheniprazine (2.5 mg/kg intraperitoneally) and clorgyline (5 mg/kg intraperitoneally) in serotoninergic synaptosomes from mouse brain was not antagonized by pretreatment of the animals with norzimelidine (20 mg/kg intraperitoneally). The partial preventing effect of α‐ethyl‐4‐methyl‐m‐tyramine (H 75/12) (2× 50 mg/kg intraperitoneally) was, on the other hand, antagonized by norzimelidine. These results do not support the hypothesis that non‐hydroxylated tryptamines and 4‐chloroamphetamine ar

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1980.tb02453.x

出版商:Blackwell Publishing Ltd    

年代:1980

数据来源: WILEY

摘要:

AbstractPlacental transfer and foetal distribution of3H‐ouabain were studied in eight pregnant women undergoing legal termination of pregnancy during the first half of gestation. The3H activity in maternal and foetal plasma, in foetal tissues and amniotic fluid was estimated using the oxidation method. The intactness of the labelled drug was determined by thin‐layer chromatography.3H‐ouabain rapidly disappeared from the maternal blood‐stream, and a measurable amount of3H activity was already present in the umbilical blood of the foetus two min. after the administration of the drug into the maternal blood. The foetal plasma3H values were lower than the maternal values during the time interval 2 to 120 min. after injection, and the foetal3H plasma concentrations approximated the maternal values five hours after drug administration. The3H concentrations found in the amniotic fluid were lower than those in the corresponding maternal or foetal plasma samples. The distribution of ouabain in the foetal tissues was relatively uniform, with the highest3H concentrations foundin the heart and placenta, the lowest in the brain. The results suggest that the human foetal heart has some capacity to bind ouabain even during the first half of ge

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1980.tb02454.x

出版商:Blackwell Publishing Ltd    

年代:1980

数据来源: WILEY

摘要:

AbstractThe effects of seasonal feeding on the structure and function of the hepatic microsomes of the reindeer were studied. In native microsomes the protein content did not vary depending on seasonal feeding, but there was a slight modification of the lipid moiety. The sensitivity of microsomes to membrane treatments changed from season to season. Seasonal feeding did not affect the hepatic cytochromecreductase activity. However, the poor winter food depressed UDPglucuronosyltransferase activity to one third of that after summer feeding. The UDPglucuronosyltransferase activity was lower in both native and treated microsomes. No differences were found in serum activities of aspartate or alanine aminotransferase although there were changes in the structure and function of hepatocytes. The poor winter feeding of the reindeer decreases their capacity to glucuronate foreign compounds and this is mediated by structural modification on the hepatic endoplasmic reticulum.

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1980.tb02455.x

出版商:Blackwell Publishing Ltd    

年代:1980

数据来源: WILEY

摘要:

AbstractThe ototoxic effects of RU 25434, a new semi‐synthetic aminoglycoside antibiotic, were compared to those of amikacin and neomycin. Experiments were performed in adult and new‐born guinea‐pigs, ototoxicity being assessed by Preyer's reflex response and the measurement of the cochlear microphonic potentials at the end of treatment. The well known ototoxicity of neomycin was observed and RU 25434 appeared to be relatively less toxic than amikacin. The use of new‐born guinea‐pigs seems to be particularly suitable for this type of study because of their apparent sensitivity to ot

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1980.tb02456.x

出版商:Blackwell Publishing Ltd    

年代:1980

数据来源: WILEY

摘要:

AbstractA study was made of the effect of unilateral injection of taurine into the substantia nigra on the behaviour of rats. Taurine (10–200 μg) induced a dose‐dependent contralateral circling behaviour. The maximum intensity of circling after doses of 100–200 μg of taurine was reached within 10 min. and the circling lasted for about 4–5 hrs. There was neither ipsilateral circling nor stereotyped behaviour. Intranigral injection of isethionic acid, a metabolite of taurine, induced weak ipsilateral circling of short duration. Pretreatment with bicuculline (3 mg/kg intraperitoneally) or strychnine (0.25 mg/kg intraperitoneally) significantly inhibited the taurine‐induced circling. A dose of 1 mg/kg but not of 0.5 mg/kg of haloperidol (subcutaneously) significantly decreased the intensity of the taurine‐induced circling. Pretreatment with atropine (10 mg/kg intraperitoneally) had no significant effect on the circling behaviour. Besides the dopaminergic nigrostriatal pathway, the non‐dopaminergic nigral output pathways also seem to be involved in the taurine‐induced circling behaviour. The results show that taurine may play some role in the function of the

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1980.tb02457.x

出版商:Blackwell Publishing Ltd    

年代:1980

数据来源: WILEY