摘要:

The first issue of Acta pharmacologica et toxicologica was circulated on May 5th, 1945, the very day on which World War II ended in Denmark. The journal is the official publication medium of the Scandinavian Pharmacological Societies. The societies are also represented by associate editors in the editorial board of Pharmacological Reviews. On the happy occasion of the anniversary, we were pleased to receive the following congratulation address from the editor of Pharmacological Reviews, James A. Bain, Ph.D., past president of the International Union of Pharmacology, and Professor of Pharmacology, School of Medicine Emory University, Atlanta, Georgia 30322, U.S.A.Jens S. Schou

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1985.tb01302.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

Female rats were given 16% ethanol solution as the sole liquid during the entire period of gestation. At birth the offspring was removed and reared by foster dams consuming normal tap water. At adult age the female offspring showed deficiencies in their maternal behaviour; they built nests of poor quality and they displayed prolonged times for retrieving pups placed outside the nest. In the whole brains of the prenatally ethanol‐exposed females a decreased serotonin synthesis was observed. The offspring of the prenatally ethanol exposed mothers did not show any signs of disturbances in physical or behavioural developmen

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1985.tb01303.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

Female rats were given 16% ethanol solution as the sole liquid during the entire period of gestation. At birth the offspring was removed and reared by foster dams consuming normal tap water. The development of sensory motor behaviour and emotional reactions was delayed by 1–2 days in the prenatally ethanol exposed pups as assessed by tests on body righting, acoustic startle response, air righting, rearing and ultrasonic vocalization. In the open‐field test the normally occurring behavioural difference between the sexes was not found in the prenatally ethanol exposed pups. Both sexes of the ethanol exposed pups behaved like the female controls suggesting deficient masculinization of the ethanol exposed male pups during foetal age. Biochemical analysis of the brains showed a decreased synthesis of serotonin and dopam

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1985.tb01304.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

Psychomotor effects of alprazolam (AZ) and diazepam (DZ) were compared in a controlled double‐blind and cross‐over trial in 24 student volunteers, who received, three times daily, placebo for the first 4 days, then an active drug (AZ) 0.25 mg or DZ 5 mg) for 7 days, and again placebo for 3 days. After a 3 week wash‐out period the procedure was repeated with the comparative drug. Objective and subjective measurements were made on day 3 (placebo), on days 4 and 10 (active drug) and on days 11, 12 and 13 (follow‐up placebo). Baseline levels were measured in the morning, a capsule was taken, and the tests were repeated 2 hours and 8 hours later. Blood samples were taken in the afternoon of day 10 for the bioassay of serum benzodiazepine concentrations. Single doses of both AZ 0.25 mg and DZ 5 mg showed similar degree of impairment in several objective tests. At the end of the 7‐day maintenance DZ (15 mg daily) proved significantly more sedative and impaired more psychomotor performance than AZ (0.75 mg daily) did. Improvement of the complex test performances (a learning effect) was counteracted by DZ more than by AZ. No actual development of tolerance was demonstrated after either drug. During the follow‐up placebo phase, DZ showed more objective residual effects than AZ. The Maddox wing test (exophoria) showed a significant DZ effect to be still present on the third post‐treatment day. However, during the follow‐up period subjects reported subjectively more sedation and clumsiness after AZ than after DZ, but this was not associated with impairment of o

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1985.tb01305.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

Development of cross‐tolerance between lorazepam and four other benzodiazepines (BZ) was studied in two trials by measuring objective psychomotor performance and by subjective assessments. In trial I, nitrazepam 10 mg (NZ), temazepam 20 mg (TZ) or placebo were administered to 14 healthy students for 10 consecutive nights. After each pretreatment, psychomotor impairment by the challenge dose of lorazepam 3 mg (LZ) was measured. In trial II, responses to LZ after pretreatment with diazepam 5 mg (DZ) (8 subjects) or alprazolam 0.25 mg (AZ) (10 subjects), both t.i.d., were compared to LZ responses measured after one‐month wash‐out period. In trial I no cross‐tolerance between BZs was found in objective tests, and LZ induced exophoria was even increased. However, the subjects rated LZ to cause less drowsiness after pretreatment with NZ in a situation where the manifestation of cross‐tolerance was facilitated by ingestion of caffeine. In trial II a clear but task‐dependent development of tolerance to the challenge dose of LZ was documented. One‐week pretreatment with DZ reduced subjects responses to LZ. The total serum BZ activity bioassayed by radioreceptor method after intake of LZ was significantly (P<0.05) higher after pretreatment with DZ than in the end of wash‐out period. Thus a functional cross‐tolerance was documented on complex tasks after the subjects have been continuously workin

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1985.tb01306.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

The stimulatory influence of ammonium sulphate on adenylate cyclase activity has been investigated. By competition binding experiments on the β‐adrenergic stimulatory receptor in rat myocardial membranes, no influence could be detected of ammonium sulphate neither in receptor coupling to the stimulatory guanine nucleotide binding protein nor in the GTP‐induced uncoupling. In order to detect an impaired inhibition instead of an increased stimulation of adenylate cyclase activity by ammonium sulphate the investigation was extended to inhibitory receptors. The same type of effect by ammonium sulphate was detected on both the muscarinic cholinergic receptor in rat myocardial membranes as well as on the α2‐adrenergic receptor in human platelets. The influence of ammonium sulphate noted in competition binding studies and off‐kinetics experiments was GTP‐like, i.e. causing a decrease in agonist‐receptor affinity leaving all the inhibitory receptors in the low affinity state. In conclusion, this paper indicates that the observed stimulatory effect of ammonium sulphate is exerted by the ammonium ion on the inhibitory guanine nucleotide binding protein, impairing the negative control of adenylate cyc

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1985.tb01307.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

The contractile responses of an α‐adrenoceptor agonist, phenylephrine, and of histamine were compared in the intimal and medial smooth muscle layers of the pig aortic arch. Further, the relaxant effects evoked by some compounds influencing the cyclic AMP system were compared in the two muscle layers, as well as their effects on the cyclic AMP content and phosphodiesterase activity. Phenylephrine and histamine induced contraction of the smooth muscle layers. The increase in tension was faster in the intimal than in the medial layer. The α‐adrenoceptor agonist phenylephrine was a more potent contractile agent in the intimal than in the medial smooth muscle. With histamine, no significant difference in the dose‐response curves between the two muscle layers was found. Histamine‐contracted muscle preparations were relaxed in a dose‐dependent manner by the phosphodiesterase‐inhibiting compound 3‐isobutyl‐1‐methylxanthine (MIX) and by 8‐bromo‐cyclic AMP. The two substances were more potent relaxants in the medial than in the intimal smooth muscle layer. The content of cyclic AMP in the intimal and the medial smooth muscle was increased by MIX. Isoprenaline had no relaxing effect on the muscle preparations and did not change the content of cyclic AMP. There were no differences in the basal levels of cyclic AMP in the intima and media. Vmaxof phosphodiesterase activities differed, however, between the two preparations. This study demonstrates that the intimal layer is characterized by a larger contractile responsiveness to phenylephrine and a lower relaxant response to compounds influencing the cyclic AMP‐system than

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1985.tb01308.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

The effect of hepatic glutathione (GSH) depletion and enzyme induction on hepatic glutathione S‐transferase (GST) activity, biliary excretion of GSH, methyl mercury, cadmium and zinc was studied in rats. The GSH depletors, methyl iodide and diethyl maleate, did not influence hepatic GST activity but, depending on the substrate used, benzo(a)pyrene, phenobarbital, pregnenolone‐16α‐carbonitrile (PCN) andtrans‐stilbene oxide (TSO) increased it by 16–33, 44–89, 53–97 and 208–279%, respectively. GSH depletors decreased (‐ 88%), benzo(a)pyrene and TSO did not affect, phenobarbital and PCN increased (+113 and + 149%) the transport of GSH into bile. The biliary excretion of methyl mercury, cadmium and zinc was reduced by GSH depletors (‐97, ‐74 and ‐93%), and enhanced by phenobarbital (+139, +280 and + 220%) and PCN (+150, +121 and +160%). Treatment with benzo(a)pyrene and TSO did not affect the excretion of methyl mercury and zinc into bile, but decreased that of cadmium. These results do not provide evidence for the role of hepatic GST but strongly support the importance of biliary GSH excretion in the hepatobiliary transport of methyl mercury, cadmium and zinc. It is assumed that phenobarbital and PCN enhance the biliary excretion of these metals by increasing the transport of GSH, the carrier mole

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1985.tb01309.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

The possibility of development of adaptation to intestinal adverse effects of auranofin (AF), a gold‐containing anti‐arthritic drug, was investigated in rats. Groups of 6 rats received orally 0.0, 2.5 or 10.0 mg AF/kg daily for one week, and 20.0 mg AF/kg daily the next week. During the first week all animals had normal stools. During the second week, those on 0.0 or 2.5 mg AF/kg the preceeding week developed persistent loose stools, whereas those on 10.0 mg AF/kg the preceeding week did not. At the end of the second week, no differences in the intestinal cytosolic gold concentrations were detected, which could be related to the dose regimen or the loose stools. Gel filtration profiles of gold from intestinal, liver and kidney cytosols following AF treatment, were compared with gold profiles followingin vitroincubation of AF with cytosols obtained from non‐treated rats. In thein vivosituation, but notin vitro, gold peaked with proteins of mol. wt. about 10,000 in the small intestine and kidneys. Up to 20% of the cytosolic gold was recovered in these fractions in the small intestine. These proteins eluted slightly different from metallothionein on gel filtration. The cellular mechanisms involved in the demonstrated adaptation to intestinal adverse effects from AF, are not clear, judged from the present

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1985.tb01310.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

The creatine kinase (CK) method, which is based on differences in CK activity at injection sites and in control tissue, was used for quantitation of local tissue damage after intramuscular injection of varying volumes and preparations in rabbits and pigs. Injections were given in the central part of the longissimus dorsi muscle. Three days after the injections the animals were killed and the arbitrary amounts of tissue without CK were calculated from the CK activity in muscle tissue at the injection sites and in control tissue. Determination of tissue damage by the CK method was in good agreement with macroscopic and microscopic changes, whether a well demarcated necrotic area or little or no necrosis was found at the injection site. Tissue damage was proportional to injection volumes between 0.25 and 1 ml in rabbits and 0.5 and 3 ml in pigs. In rabbits tissue damage per injected ml was found to be more than twice the damage seen in pigs. It is concluded that the CK method is a reliable method for quantitation of local tissue damage after intramuscular injections and that injection of even small volumes of 0.25–0.5 ml in the longissimus dorsi muscle of rabbits is a sensitive test of the local toxicity of drug

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1985.tb01311.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY