摘要:

Abstract:Aminophylline in the doses 6.31 · 10−5mol kg−1and 2.37 · 10−4mol kg−1(corresponding to 13.8 and 52.0 mg kg−1respectively) and 3‐methylxanthine 2.37 · 10−4mol kg−1(39.4 mg kg−1) was administered to guinea pigs by intravenous bolus injection, n = 7, 10, and 6, respectively. The shape of semilogarithmic plots of all measured plasma theophylline concentrations versus time was compatible with the use of an open 2‐compartment pharmacokinetic model assuming first‐order distribution and elimination processes, but in the comparison of the mean values of the pharmacokinetic parameters obtained after the administration of the low and the high theophylline dose, statistical analysis by Student's t‐test showed β and V1to be significantly altered (low dose: β=0.00338 min.−1, V1= 392 ml kg−1; high dose: β = 0.00198 min.−1, V1= 528 ml kg−1; P<0.05). Following the administration of 3‐methylxanthine, the observed plasma concentration time course of this pharmacologically active theophylline metabolite could be adequately described be means of the 2‐compartment open model. The administered 3‐methylxanthine was eliminated unchanged with a first‐order rate constant ten times larger‐than the total elimination rate constant of theophylline itself, the latter being observed after the administration of the equimolar dose of aminophylline (kel 3mx= 0.029 min.−1, kel theophylline= 0.00293 min.−1). Clearance was calculated to 14.4 ml kg−1min.−1for 3‐methylxanthine and 1.50 ml kg−1min.−1for theophylline. When aminophylline 2.37 · 10−4mol kg−1had been administered, 3‐methylxanthine was renally eliminated at a constant rate for the first hours after the injection, but it did only

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1981.tb01579.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Abstract:Following intravenous bolus injection of theophylline 2.37.10−4mol kg−1to guinea pigs (administered as aminophylline 52.0 mg kg−1), the elimination of the dose was more rapid in a group of 8 guinea pigs that had received theophylline 2.02 · 10−4mol kg−1(aminophylline 44.3 mg kg−1) intraperitoneally twice daily for 12 days prior to the experiment than in a group of 10 non‐pretreated guinea pigs of the same age. The difference was statistically significant in Student's t‐test (P<0.02). The mean values in the group of pretreated animals were: kel0.00457 min.−1, β 0.00296 min.−1, clearance 2.04 ml kg−1min.−1, Vdβ693 ml kg−1. By way of comparison, the values obtained in non‐pretreated guinea pigs were: kel0.00293 min.−1, β 0.00198 min.−1, clearance 1.50 ml kg−1min.−1, Vdβ757 ml kg−1. This result suggests enzyme induction to occur. The pharmacologically active theophylline metabolite 3‐methylxanthine did not accumulate in the plasma during the long‐term theophylline administration. The general plasma concentration level was 0–1.8.10−8mol ml−1(0–3 μg ml−1). In 5 percent of the samples were detected concentrations in the range 1.8 · 10−8‐7.2 · 10

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1981.tb01580.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Abstract:Simultaneous administration of terbutaline and theophylline to guinea pigs did not cause significant alterations of the pharmacokinetic properties of any of the drugs. Terbutaline sulphate 24 μg kg−1and aminophylline 52 mg kg−1(7.42.10−8and 2.37.10−4mol kg−1respectively) were given by a bolus intravenous injection, producing plasma concentrations in the range 0–15 ng terbutaline sulphate per ml (0–46 nanomol 1−1) and 10–85μg theophylline per ml (50–429 μmol 1−1). Pharmacokinetic analyses of time courses of plasma concentrations of intact drugs and investigations of tissue distribution 1 hour after the administration were performed. The results showed a weak, statistically insignificant trend of the peripheral compartment of the 2‐compartment model to sequester a larger fraction of the drugs when these were a

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1981.tb01581.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Abstract:Pigmented rats were kept under different light/darkness patterns for 5–12 days. The response of the iris sphincter in enucleated eyes was tested with pilocarpine as a standard stimulus. The eyes were either decorneated or intact. The maximum response (no subsensitivity) was obtained after continuous darkness and the minimum (maximum subsensitivity) after continuous light. Six hours of light and one block of 18 hours of darkness per day caused distinct subsensitivity, but less than if the light was interrupted by six 3‐hour darkness periods. Further subdivision of the light into twelve 30‐min. periods made no difference. One 18‐hour block of light followed by 6 hours of darkness caused less subsensitivity than continuous light. Subdividing the darkness into six 1‐hour periods made no significant d

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1981.tb01582.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Abstract:Exposure of the Indian catfish (Heteropneustes fossilis) to a high sublethal concentration of 5.6 p.p.m. (0.8 of the 96 hr LC50) of methyl parathion for 3,6,12,48, and 96 hrs affected carbohydrate metabolism. Muscle glycogen levels decreased significantly at 3,6,12 and 96 hrs; liver glycogen content declined at 6 hrs but there was a resynthesis of hepatic glycogen stores at 12 hrs. Blood glucose levels in fish were elevated at 3 and 6 hrs. Mean values for blood pyruvate were elevated significantly at 6,12, and 96 hrs. Blood lactate level was elevated at 3 hrs but hypolactaemia resulted at 48 and 96 hrs in pesticide‐treated fish. The observed effects of methyl parathion on carbohydrate metabolism in fish are discussed in relation to acute stress syndrome. Measurement of carbohydrate metabolites in fish for 3 hrs or longer could prove useful as a rapid method for evaluating toxicity of pesticides and other toxicant

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1981.tb01583.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Abstract:In urethane‐anaesthetized guinea‐pigs, the effect of theophylline (theo) on heart rate, arterial blood pressure, respiration rate and limb movements were recorded. Continuous intravenous infusion of theo initially increased the respiratory and heart rates and lowered the arterial blood pressure. After infusion of about 50 mg/kg of theo, the cardiovascular effects reached a maximum and were then only slightly changed until the terminal stage. A tonic stretching of the limbs (at 155 ± 15 mg/kg) preceded generalized seizures of clonic tonic convulsions which were recorded after infusion of 367 ± 25 mg/kg of theo. At this stage, respiration was highly irregular. PaO2started to fall and PaCO2to rise, while a plasma acidosis developed rapidly. The convulsions progressed in frequency and intensity and were terminally associated with respiratory and cardiovascular collapse. The convulsive effects of theophylline were similar to those observed in conscious guinea‐pigs after 250 mg/kg of theo orally. The present findings agree with the view that the convulsive effect is a primary life‐threatening action of theophylline. The method described may be of use in the search for new, less toxic xanth

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1981.tb01584.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Abstract:Binding of3H‐enkephalinamide and3H‐naloxone to P2‐fractions of whole rat brain homogenate displayed saturable, stereospecific binding to receptor sites with at least two binding sites for3H‐met‐enkephalinamide (type I: KD= 0.4 nM and Bmax= 35 fmol/mg protein; type II: KD= 5.7 nM and Bmax= 57 fmol/mg protein) and for3H‐naloxone (type I: KD= 1.5 nM and Bmax= 40 fmol/mg protein; type II: KD= 51 nM and Bmax= 255 fmol/mg protein), β‐endorphin and met‐ and leu‐enkephalin produced a concentration‐dependent inhibition of3H‐met‐enkephalinamide and3H‐naloxone binding with dissociation constants in the nanomolar range, but with very different displacement curves. Purified porcine ACTH (1–39) displaced both3H‐met‐enkephalinamide and3H‐naloxone with dissociation constants of 3.4 × 10‐ Mand 1.8 × 10−6M, respectively. The synthetic congeners, ACTH (1–32) and to a lesser extent ACTH (1–28) and ACTH (1–24) showed a similar effect, whereas other fragments of ACTH were inactive in concentrations ranging from 10−10to 10−6M. In the same concentration range cholecystokinin congeners (CCK‐8 and CCK‐4) were without effect. Since ACTH immunoreactive nerves seem also to contain β‐endorphin and furthermore, to show a partially overlapping distribution with the enkephalinergic systems it is possible that the binding of ACTH fr

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1981.tb01585.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Abstract:The pro‐inflammatory tigliane esters 12‐deoxyphorbolphenylacetate (12‐DOPPA) and 12‐deoxy‐phorbolphenylacetate‐20‐acetate (12‐DOPPAA) at a dose of 0.1μg induced erythema in the mouse ear. Observations of ear redness were made both two and four hours after application. Indomethacin was only partly successful as an antagonist since 10% inhibition of 12‐DOPPA and no inhibition of 12‐DOPPAA induced erythema was produced four hours after application. The free radical scavengers, phenol, thioanisole and sodium benzoate all produced less than 30% inhibition of 12‐DOPPA induced erythema and less than 15% inhibition of 12‐DOPPAA, whereas aminopyrine produced 70% and 25% inhibition of 12‐DOPPA and 12‐DOPPAA respectively. The fact that free radical scavengers (with the exception of aminopyrine) and indomethacin, failed to markedly change the mouse ear reaction to 12‐deoxyphorbol esters, indicated that this erythema is not entirely mediated via cyclooxygenase products. Mepyramine and cyproheptadine also failed to inhibit the erythema, whereas hydrocortisone produced a 55% inhibition of the 12‐DOPPA and a 20% inhibition of the 12‐DOPPAA reaction. The membrane stabilising agents trifluoperazine, promethazine, imipramine and desmethylimipra‐mine were the most successful compounds used in inhibiting both 12‐DOPPA and 12‐DOPPAA induced erythema. In addition propranolol, which inhibits stimulus activation of phospholipase A2, produced 70% and 55% inhibition of the reactio

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1981.tb01586.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Abstract:The kinetics of citalopram were studied in a group of volunteers after oral (8 subjects) and intravenous (4 subjects) single doses and repeated oral administration (7 subjects). Inter‐ and intraindividual variation was limited and linearity of kinetics indicated. Systemic and apparent oral clearance estimates (mean 0.42 1 plasma/min.) were similar, indicating roughly complete systemic availability. The presence of unchanged drug in urine, corresponding to 1/7 of the dose, suggests elimination by renal as well as hepatic processes. The data from the intravenous test revealed two compartment kinetics; the total volume of distribution was estimated to about 11501 and that of the central compartment to 1751. Upon repeated administration steady‐state conditions were generally achieved after one week in agreement with the 33 hrs half‐life of elimination. Citalopram peak concentrations were reached within 2–4 hrs after the daily dose and maximally two‐fold variation was recorded in the 24 hrs dose interval. The levels of a main pharmacodynamically active metabolite were roughly half as high as the dr

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1981.tb01587.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Abstract:Rats were fed a lithium‐containing diet for five weeks (40 mmol LiCl/kg fodder). Plasma lithium concentration was 0.44 mmol Li+/1 plasma. The synaptosomes were isolated and incubated with3H‐glucosamine for 60 min. The glycopeptides and the gangliosides were extracted and the sialic acid content and the3H‐sialic acid content were measured. The lithium treatment produced an increase in the synaptosomal glycopeptide content. The sialic acid content was simultaneously increased in glycopeptides as well as gangliosides. The specific activity of sialic acid was reduced to 75% of the control value in the sialoglycopeptide fra

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1981.tb01588.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY