摘要:

Abstract:Studies of muscarinic receptor concentration and comparative binding assays of agonists and antagonists are presently donein vitroby incubation and measurement of the binding to tissue homogenates of the radiolabeled potent antagonists3H‐scopolamine or3H‐quinuclidinyl benzilate. We have developed a technique based on gas chromatography ‐ mass spectrometry that allows studies of the muscarinic receptor concentration to be performedin vivounder physiologic conditions. By injecting the optical antipodes of atropine, D‐ and L‐hyoscyamine separately in mice and following their kinetics in different parts of the brain it was possible to separate the specific receptor binding of the active antipode L‐hyoscyamine from that of the inactive antipode D‐hyoscyamine, representing unspecific binding. Two hrs after the administration of L‐hyoscyamine, 2 mg/kg intravenously, its concentration in brain was found to represent “maximum” specific binding. The physiological significance of specifically bound L‐hyoscyamine was tested on its blocking effect on oxotre

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1987.tb01719.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Abstract:Hepatic and cutaneous microsomal hydroxylating and conjugating enzymes from female and male NMRInu/numice were analyzed, and the response of these enzymes to repeated exposures with 3‐methylcholanthrene were studied. Sex differences were observed in basal activities of hydroxylating enzymes. These differences were not the same in the liver as in the skin and were reversed in female and male. Activity ratios of hepatic and cutaneous hydroxylating enzymes were between 40‐200. The ratios between hydroxylating and conjugating enzymes were much lower in the skin than in liver. Furthermore the ratios were depending on hydroxylating enzymes. 3‐Methylcholanthrene treatment increased both hydroxylating and conjugating enzymes in the liver and in the skin. Again, there were sex differences in the induction pattern, and also the induction in the liver was unrelated to that in the skin. There was no correlation in induction between hydroxylating and conjugating en

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1987.tb01720.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Abstract:The supplementation of vitamin‐B complex reduces lead intoxication. With a view to identify the components of vitamin‐B complex responsible for such protection, riboflavin, calcium pentothenate, pyridoxine, nicotinamide, folic acid and cyanocobalamine were investigated for their ability, and their influence on the efficacy of disodium calcium versenate (Na2CaEDTA), to enhance the urinary excretion of lead, mobilize tissue lead and restore lead induced biological alterations in lead intoxicated rats. Folic acid and pyridoxine besides thiamine may be the responsible factors in prophylaxis of lead poisoning by vitamin B complex or in enhancing the antidotal properties of Na2CaE

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1987.tb01721.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Abstract:It is generally accepted that there are at least three different subtypes of muscarinic cholinoceptors, pirenzepine being considered a selective M1antagonist. In the present study, a number of different types of psychotropic drugs have been compared with pirenzepine and atropine as reference antimuscarinic drugs regarding their affinities for rat brain muscarinic cholinoceptors with the help ofin vitroreceptor binding studies. The most potent drugs, inhibiting3H‐1‐quinuclidinyl benzilate (3H‐QNB) binding at subnanomolar concentrations, were the antimuscarinic drugs scopolamine and atropine. Biperiden, promethazine, pirenzepine and some tricyclic antidepressants (amitriptyline, doxepin) were the next potent drugs, with IC50‐values between 8.4 nM and 190 nM. The inhibition curves were steep and parallel giving Hill coefficients close to unity in all but two drugs studied. These exceptions were biperiden and pirenzepine both with Hill coefficients about 0.55. Thus, in addition to pirenzepine also biperiden seems to bind to the M1receptor selectively. Additional receptor and functional studies are warranted to further elucidate the possible similarities of these tw

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1987.tb01722.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Abstract:Nomifensine, in contrast to all other antidepressants, inhibits the neuronal uptake of dopamine. The effect of this drug (10 mg/kg intraperitoneally) on the metabolism of dopamine, serotonin and noradrenaline was studied in the rat brain. After 1.5 hours, nomifensine increased the concentrations of homovanillic acid (HVA) in corpus striatum and total (free and conjugated) 3‐methoxy, 4‐hydroxyphenylglycol (MOPEG) in mesencephalon, but had no effect on the 5‐hydroxyindoleacetic acid (5‐HIAA) in pons/medulla oblongata and mesencephalon. The effect was identical with that of desipramine (25 mg/kg) on MOPEG and of imipramine (25 mg/kg) on 5‐HIAA. Two methods ordinarily used for estimating turnover rates of monoamines were compared: accumulation of acid metabolites after probenecid (measuring efflux of metabolites from the brain) and accumulation of monoamine precursors after decarboxylase inhibition (measuring amine synthesis). The efflux was reduced for 5‐HIAA and MOPEG but increased for HVA after nomifensine. Imipramine had the same effect on 5‐HIAA and desipramine on MOPEG. Desipramine decreased the efflux of HVA from corpus striatum. In contrast, nomifensine did not change the synthesis of noradrenaline and serotonin significantly. Imipramine reduced the synthesis of serotonin in pons/medulla oblongata. In corpus striatum nomifensine, unlike imipramine, increased the concentration of 5‐HIAA and synthesis of serotonin in spite of a decrease in efflux, probably because of a secondary effect from the dopaminergic action. The conclusion was made that there were more than one compartment of monoamine metabolites. The antidepressants could to some extent lead to a shift in the metabolism to sites more distant to the tran

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1987.tb01723.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1987.tb01724.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY