Pub Date : 2009-03-26DOI: 10.1111/J.1600-0773.1972.TB03606.X
K. Overø
: For the plasma analysis of drugs containing primary or secondary amino groups the method of HAMMER & BRODIE (1967) has been widely used. By this technique amines are isolated by extraction and coupled with 3H-acetic anhydride. After removal of excess labelling agent, the amount of labelled coupling product is assayed by liquid scintillation counting. The possibility of masking primary amines by adding salicylic aldehyde to the hexane phase in the first extraction step of this method has been investigated. The presence of 0.1 M salicylic aldehyde was found to reduce considerably the amount of primary amine measured as 3H-amide, while secondary amines were only slightly influenced. Thus increased specifity for secondary amines was achieved. The practical importance of the modified method was illustrated by experiments on plasma from rats given nortriptyline and human subjects given Lu 5-003, a bicyclic thymoleptic. In the former case the modified method is of less importance, since no primary amine metabolite is present - in the latter case, however, it would be advantageous, because the corresponding primary amine is present as a metabolite in plasma.
{"title":"Increased specificity of the 3 H-acetic anhydride coupling method for plasma analysis of drugs containing secondary amino groups.","authors":"K. Overø","doi":"10.1111/J.1600-0773.1972.TB03606.X","DOIUrl":"https://doi.org/10.1111/J.1600-0773.1972.TB03606.X","url":null,"abstract":": For the plasma analysis of drugs containing primary or secondary amino groups the method of HAMMER & BRODIE (1967) has been widely used. By this technique amines are isolated by extraction and coupled with 3H-acetic anhydride. After removal of excess labelling agent, the amount of labelled coupling product is assayed by liquid scintillation counting. The possibility of masking primary amines by adding salicylic aldehyde to the hexane phase in the first extraction step of this method has been investigated. The presence of 0.1 M salicylic aldehyde was found to reduce considerably the amount of primary amine measured as 3H-amide, while secondary amines were only slightly influenced. Thus increased specifity for secondary amines was achieved. The practical importance of the modified method was illustrated by experiments on plasma from rats given nortriptyline and human subjects given Lu 5-003, a bicyclic thymoleptic. In the former case the modified method is of less importance, since no primary amine metabolite is present - in the latter case, however, it would be advantageous, because the corresponding primary amine is present as a metabolite in plasma.","PeriodicalId":6972,"journal":{"name":"Acta pharmacologica et toxicologica","volume":"70 1","pages":"433-40"},"PeriodicalIF":0.0,"publicationDate":"2009-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90074502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2009-03-13DOI: 10.1111/J.1600-0773.1971.TB00623.X
A. Frøslie
The six compounds DNOC, DNBP, 6-ANOC, 6-ANBP, 6-AcANOC and 6-AcANBP were investigated for their methaemoglobin-forming effect on bovine erythrocytes in vitro, and also, for comparative reasons, on erythrocytes from horse, dog, pig and man. Only the amino-nitrophenols showed any methaemoglobin-forming effect. The activity was somewhat different for the different species, the haemoglobin in dog erythrocytes in particular being more easily oxidized than the haemoglobin in erythrocytes from the other species. Differences were also recorded between the two amino-nitrophenols, 6-ANOC being more active than 6-ANBP in the bovine erythrocytes, while 6-ANBP was more active in the pig and horse erythrocytes. In the dog and man there was a little difference between the two substances. The results are discussed in relation to the di-nitrophenols' comparative toxicology, in particular in relation to the ruminants' special position as regards the metabolism and the toxicity of these substances.
{"title":"Methaemoglobin formation in vitro by 6-amino metabolites of DNOC and DNBP.","authors":"A. Frøslie","doi":"10.1111/J.1600-0773.1971.TB00623.X","DOIUrl":"https://doi.org/10.1111/J.1600-0773.1971.TB00623.X","url":null,"abstract":"The six compounds DNOC, DNBP, 6-ANOC, 6-ANBP, 6-AcANOC and 6-AcANBP were investigated for their methaemoglobin-forming effect on bovine erythrocytes in vitro, and also, for comparative reasons, on erythrocytes from horse, dog, pig and man. Only the amino-nitrophenols showed any methaemoglobin-forming effect. The activity was somewhat different for the different species, the haemoglobin in dog erythrocytes in particular being more easily oxidized than the haemoglobin in erythrocytes from the other species. Differences were also recorded between the two amino-nitrophenols, 6-ANOC being more active than 6-ANBP in the bovine erythrocytes, while 6-ANBP was more active in the pig and horse erythrocytes. In the dog and man there was a little difference between the two substances. The results are discussed in relation to the di-nitrophenols' comparative toxicology, in particular in relation to the ruminants' special position as regards the metabolism and the toxicity of these substances.","PeriodicalId":6972,"journal":{"name":"Acta pharmacologica et toxicologica","volume":"1606 1","pages":"490-8"},"PeriodicalIF":0.0,"publicationDate":"2009-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86510679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2009-03-13DOI: 10.1111/J.1600-0773.1973.TB01469.X
A. Frøslie
{"title":"Methaemoglobin formation by diamino metabolities of DNOC and DNBP.","authors":"A. Frøslie","doi":"10.1111/J.1600-0773.1973.TB01469.X","DOIUrl":"https://doi.org/10.1111/J.1600-0773.1973.TB01469.X","url":null,"abstract":"","PeriodicalId":6972,"journal":{"name":"Acta pharmacologica et toxicologica","volume":"29 1","pages":"257-65"},"PeriodicalIF":0.0,"publicationDate":"2009-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74920760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2009-03-13DOI: 10.1111/J.1600-0773.1977.TB02105.X
J. Jonsson
The liver microsomal p-hydroxylation of amphetamine to parahydroxyamphetamine (pOHA) was dependent on NADP and inhibited by carbon monoxide indicating the involvement of cytochrome P-450, SKF 525-A, fenfluramine and desmethylimipramine were the most effective inhibitors of this pathway of amphetamine metabolism. Repeated administraion of phenobarbital resulted in reduced p-hydroxylation of amphetamine in vitro. Chronic administration of amphetamine reduced the microsomal p-hydroxylation of amphetamine without apparent changes in the cytochrome P-450 levels or in the activity of NADPH-cytochrome c reductase. The aromatic hydroxylation of aniline and the demethylation of ethylmorphine was not affected by this treatment. However, the 455 nm complex formed during the microsomal metabolism of N-hydroxy-amphetamine was increased by the long-term administration of amphetamine. These results indicate some pecularities of the in vitro hydroxylation of amphetamine by rat liver microsomes. Amphetamine disappeared from the perfusate of the perfused liver at the same rate in rats given a single dose of amphetamine and in rats given amphetamine orally for four weeks. The excretion of pOHA and its conjugate increased at 60 and 90 min. and 30, 60 and 90 min. respectively in the perfusate of the same experiment as compared to the controls. The total excretion of radioactive amphetamine metabolites at the end of the perfusion was increased in the perfusate and reduced in the bile compared to the control experiment.
{"title":"On the aromatic hydroxylation of amphetamine in rat liver microsomes and perfused liver preparations: effects of long-term administration.","authors":"J. Jonsson","doi":"10.1111/J.1600-0773.1977.TB02105.X","DOIUrl":"https://doi.org/10.1111/J.1600-0773.1977.TB02105.X","url":null,"abstract":"The liver microsomal p-hydroxylation of amphetamine to parahydroxyamphetamine (pOHA) was dependent on NADP and inhibited by carbon monoxide indicating the involvement of cytochrome P-450, SKF 525-A, fenfluramine and desmethylimipramine were the most effective inhibitors of this pathway of amphetamine metabolism. Repeated administraion of phenobarbital resulted in reduced p-hydroxylation of amphetamine in vitro. Chronic administration of amphetamine reduced the microsomal p-hydroxylation of amphetamine without apparent changes in the cytochrome P-450 levels or in the activity of NADPH-cytochrome c reductase. The aromatic hydroxylation of aniline and the demethylation of ethylmorphine was not affected by this treatment. However, the 455 nm complex formed during the microsomal metabolism of N-hydroxy-amphetamine was increased by the long-term administration of amphetamine. These results indicate some pecularities of the in vitro hydroxylation of amphetamine by rat liver microsomes. Amphetamine disappeared from the perfusate of the perfused liver at the same rate in rats given a single dose of amphetamine and in rats given amphetamine orally for four weeks. The excretion of pOHA and its conjugate increased at 60 and 90 min. and 30, 60 and 90 min. respectively in the perfusate of the same experiment as compared to the controls. The total excretion of radioactive amphetamine metabolites at the end of the perfusion was increased in the perfusate and reduced in the bile compared to the control experiment.","PeriodicalId":6972,"journal":{"name":"Acta pharmacologica et toxicologica","volume":"6 1","pages":"517-28"},"PeriodicalIF":0.0,"publicationDate":"2009-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78610245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2009-03-13DOI: 10.1111/J.1600-0773.1977.TB02106.X
C. Persson, K. Andersson
The effects of 3-methylxanthine (3-MX), a major metabolite of theophylline in man, were studied and compared with those of theophylline in isolated preparations of human and guinea-pig airways, isolated guinea-pig hearts, and in anaesthetized cats. 3-MX was pharmacologically active, producing effects similar to those of theophylline. The guinea-pig and human airways preparations were relaxed; the rate and force of contraction of guinea-pig hearts were increased. In anaesthetized cats, 3-MX decreased the respiratory overflow and arterial blood pressure, and increased the heart rate. Theophylline was always more potent (between 1 and 5 times) than 3-MX. It is suggested that 3-MX may contribute to the effects of theophylline during long-term treatment.
{"title":"Respiratory and cardiovascular effects of 3-methylxanthine, a metabolite of theophylline.","authors":"C. Persson, K. Andersson","doi":"10.1111/J.1600-0773.1977.TB02106.X","DOIUrl":"https://doi.org/10.1111/J.1600-0773.1977.TB02106.X","url":null,"abstract":"The effects of 3-methylxanthine (3-MX), a major metabolite of theophylline in man, were studied and compared with those of theophylline in isolated preparations of human and guinea-pig airways, isolated guinea-pig hearts, and in anaesthetized cats. 3-MX was pharmacologically active, producing effects similar to those of theophylline. The guinea-pig and human airways preparations were relaxed; the rate and force of contraction of guinea-pig hearts were increased. In anaesthetized cats, 3-MX decreased the respiratory overflow and arterial blood pressure, and increased the heart rate. Theophylline was always more potent (between 1 and 5 times) than 3-MX. It is suggested that 3-MX may contribute to the effects of theophylline during long-term treatment.","PeriodicalId":6972,"journal":{"name":"Acta pharmacologica et toxicologica","volume":"35 1","pages":"529-36"},"PeriodicalIF":0.0,"publicationDate":"2009-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76532987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2009-03-13DOI: 10.1111/J.1600-0773.1981.TB03366.X
B. Fredholm
{"title":"Hormones, receptors and cyclic nucleotides. Papers presented at the 6th Scandinavian Meeting on Cyclic Nucleotide Research. Utö, May 24-26, 1981. Abstracts.","authors":"B. Fredholm","doi":"10.1111/J.1600-0773.1981.TB03366.X","DOIUrl":"https://doi.org/10.1111/J.1600-0773.1981.TB03366.X","url":null,"abstract":"","PeriodicalId":6972,"journal":{"name":"Acta pharmacologica et toxicologica","volume":"12 1","pages":"1-57"},"PeriodicalIF":0.0,"publicationDate":"2009-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89710812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2009-03-13DOI: 10.1111/J.1600-0773.1986.TB02516.X
K. Andersson, J. Abelin
{"title":"On calcium and calcium channel blockade.","authors":"K. Andersson, J. Abelin","doi":"10.1111/J.1600-0773.1986.TB02516.X","DOIUrl":"https://doi.org/10.1111/J.1600-0773.1986.TB02516.X","url":null,"abstract":"","PeriodicalId":6972,"journal":{"name":"Acta pharmacologica et toxicologica","volume":"11 1","pages":"1-204"},"PeriodicalIF":0.0,"publicationDate":"2009-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85193757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2009-03-13DOI: 10.1111/J.1600-0773.1977.TB02073.X
K. Jørgensen
The new sulphonylurea CS 476 was tested for positive iontropic effect on the isolated cat papillary muscle. Unlike tolbutamide CS 476 had no positive inotropic effect. CS 476 had no adverse effect on blood pressure in dogs, cats and rats nor on the electrocardiogram of dogs in doses up to ten times the therapeutic dose. Unlike chlorpromide CS 476 did not potentiate the effect of exogenous antidiuretic hormone in hydrated dogs. In therapeutic concentrations the drug had no effect on smooth muscle preparations. 1,000-10,000 times therapeutic concentrations had a papaverine-like effect - similar to therapeutic concentrations of tolbutamide.
{"title":"The pharmacology of a new hypoglycaemic agent N-[4-(2-(2,3-dihydrobenzo(b)furan-7-carboxamid o)-ethyl)-benzenesulphonyl]-N'-cyclohexlurea (NOVO CS 476). III. General pharmacological studies.","authors":"K. Jørgensen","doi":"10.1111/J.1600-0773.1977.TB02073.X","DOIUrl":"https://doi.org/10.1111/J.1600-0773.1977.TB02073.X","url":null,"abstract":"The new sulphonylurea CS 476 was tested for positive iontropic effect on the isolated cat papillary muscle. Unlike tolbutamide CS 476 had no positive inotropic effect. CS 476 had no adverse effect on blood pressure in dogs, cats and rats nor on the electrocardiogram of dogs in doses up to ten times the therapeutic dose. Unlike chlorpromide CS 476 did not potentiate the effect of exogenous antidiuretic hormone in hydrated dogs. In therapeutic concentrations the drug had no effect on smooth muscle preparations. 1,000-10,000 times therapeutic concentrations had a papaverine-like effect - similar to therapeutic concentrations of tolbutamide.","PeriodicalId":6972,"journal":{"name":"Acta pharmacologica et toxicologica","volume":"8 1","pages":"234-40"},"PeriodicalIF":0.0,"publicationDate":"2009-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86604488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2009-03-13DOI: 10.1111/J.1600-0773.1965.TB00358.X
J. Møller
{"title":"The tubular site of urate transport in the rabbit kidney, and the effect of probenecid on urate secretion.","authors":"J. Møller","doi":"10.1111/J.1600-0773.1965.TB00358.X","DOIUrl":"https://doi.org/10.1111/J.1600-0773.1965.TB00358.X","url":null,"abstract":"","PeriodicalId":6972,"journal":{"name":"Acta pharmacologica et toxicologica","volume":"28 1","pages":"329-36"},"PeriodicalIF":0.0,"publicationDate":"2009-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73298389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2009-03-13DOI: 10.1111/J.1600-0773.1965.TB00357.X
J. Møller
{"title":"Clearance experiments on the effect of probenecid on urate excretion in the rabbit.","authors":"J. Møller","doi":"10.1111/J.1600-0773.1965.TB00357.X","DOIUrl":"https://doi.org/10.1111/J.1600-0773.1965.TB00357.X","url":null,"abstract":"","PeriodicalId":6972,"journal":{"name":"Acta pharmacologica et toxicologica","volume":"335 1","pages":"321-8"},"PeriodicalIF":0.0,"publicationDate":"2009-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80615905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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