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  • 1
    Electronic Resource
    Electronic Resource
    The effects of chronic carbamazepine treatment on haem biosynthesis in man and rat (1988)
    Springer
    European journal of clinical pharmacology 35 (1988), S. 241-247 
    Details
    ISSN: 1432-1041
    Keywords: carbamazepine ; porphyria ; epilepsy ; haem biosynthesis ; enzyme induction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The anticonvulsant drug carbamazepine has been reported to produce a condition clinically and biochemically similar to acute intermittent porphyria (AIP). We have determined the effect of chronic carbamazepine treatment on the activities of the enzymes of haem biosynthesis in circulating blood cells and on the urinary excretion of porphyrins and their precursors in 53 epileptic patients receiving monotherapy and in 42 age- and sex-matched controls. In the patients the mean activity of leucocyte 5-aminolaevulinic acid (ALA) synthase, the rate-limiting enzyme of the pathway, was 218% of control values (p〈0.001) and ALA-dehydratase activity was reduced by 37% (p〈0.001). Circulating carbamazepine concentrations correlated negatively with ALA dehydratase (r s=−0.45;p〈0.01). Porphobilinogen deaminase and uroporphyrinogen decarboxylase appeared unaffected by carbamazepine treatment. Significant quantitative increases in the urinary excretion of porphobilinogen and total porphyrins (bothp〈0.05) accompanied the changes in enzyme activity. Similar dose-dependent effects on ALA synthase and ALA dehydratase were shown to occur in rats treated for 5 days with 3 different doses of carbamazepine. These findings further support the porphyrinogenicity of carbamazepine, but the pattern of enzyme alteration differs from that found in AIP.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00558260
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  • 2
    Electronic Resource
    Electronic Resource
    The effects of industrial lead poisoning on cytochrome P450 mediated phenazone (antipyrine) hydroxylation (1977)
    Springer
    European journal of clinical pharmacology 12 (1977), S. 235-239 
    Details
    ISSN: 1432-1041
    Keywords: phenazone ; lead ; haem biosynthesis ; cytochrome P450 ; saliva
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a group of ten male adults admitted to hospital with clinical symptoms of lead exposure, phenazone elimination rates, blood δ-amino-laevulinic acid dehydratase (ALA.D) activity, blood lead levels and haemoglobin were measured. Investigations were carried out before, immediately after and again at least 12 weeks after cessation of CaEDTA (sodium calcium edetate) chelation therapy. Following chelation, phenazone elimination rates were increased as assessed by a decrease in half life and increase in clearance. This was significant, both immediately after and 12 weeks after cessation of chelation therapy. The change in rate of phenazone metabolism was associated with improved clinical status, with lowered blood lead levels and raised haemoglobin and ALA.D activity. The results of the study suggest that the depression in phenazone elimination in lead intoxication is possibly due to depressed hepatic cytochrome P450 levels.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00609867
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  • 3
    Electronic Resource
    Electronic Resource
    The effects of bromocriptine and prolactin on porphyrin biosynthesis and morphology in the female hamster Harderian gland (1996)
    Springer
    Journal of comparative physiology 166 (1996), S. 144-149 
    Details
    ISSN: 1432-136X
    Keywords: Porphyrin ; Harderian gland ; Bromocriptine ; Prolactin ; Hamster
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Porphyrin biosynthesis was examined in the Harderian gland of the female golden hamster by fluorometric assays of gland porphyrin content and by measuring the activity of a rate-limiting enzyme for haem biosynthesis, δ-aminolaevulinic acid synthase. Both porphyrin content and enzyme activity are high in normal female glands. Enzyme activity was lowered in females ovariectomised for 6 weeks, and both enzyme activity and porphyrin content were greatly lowered in ovariectomised females given the dopamine agonist bromocriptine; this suppression could be prevented by simultaneous prolactin administration. Bromocriptine (but not ovariectomy alone) also masculinised the morphology of the Harderian gland, resulting in the appearance of type II cells and polytubular complexes; again, the simultaneous administration of prolactin prevented masculinisation. The results support the hypothesis that while androgens have an inhibitory effect on porphyrin synthesis within this model, prolactin may have a major facilitatory role.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00301178
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  • 4
    Electronic Resource
    Electronic Resource
    The effects of bromocriptine and prolactin on porphyrin biosynthesis in the Harderian gland of the male hamster, Mesocritecus auratus (1995)
    Springer
    Journal of comparative physiology 164 (1995), S. 524-529 
    Details
    ISSN: 1432-136X
    Keywords: Porphyrin ; Harderian gland ; Bromocriptine ; Prolactin ; Hamster, Mesocritecus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Porphyrin biosynthesis was examined in the Harderian gland of the male golden hamster by fluorometric assays of gland porphyrin content and by measuring the activity of a rate-limiting enzyme for haem biosynthesis, 5-aminolaevulinic acid synthase. Both porphyrin content and enzyme activity are low in normal male glands but were greatly raised in males castrated for 6 weeks. However, porphyrin synthesis remained at basal levels in castrates given the dopamine agonist bromocriptine; this suppression could be reversed by simultaneous prolactin administration, and castrated males receiving prolactin alone exhibited very high enzyme activity and porphyrin content. Bromocriptine also prevents the morphological feminisation of the Harderian gland which would normally occur after castration; again, the simultaneous administration of prolactin permits feminisation to occur. The results support the hypothesis that, while androgens have an inhibitory effect on porphyrin synthesis within this model, other factors, including prolactin, are permissive.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00261392
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