Modulation of CYP1A2 enzyme activity by indoleamines

Agúndez, José A. G.; Gallardo, Lourdes; Martı́nez, Carmen; Gervasini, Guillermo; Benı́tez, Julio

doi:10.1097/00008571-199806000-00007

Cited by 15 publications

(17 citation statements)

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“…2). Corresponding values previously reported for HLM range from as low as 2.7 M (Kobayashi et al, 1998) to 116 M (Ching et al, 2001); however, most values range between 9 and 68 M (Brosen et al, 1993;Tassaneeyakul et al, 1993;Bourrie et al, 1996;Schmider et al, 1996;Von Moltke et al, 1996a;Rodrigues et al, 1997;Agundez et al, 1998;Eagling et al, 1998;Kobayashi et al, 1999;Belle et al, 2000;Li et al, 2003) (Fig. 4).…”

Section: Resultssupporting

confidence: 59%

“…An assay for phenacetin O-deethylase for CYP1A2 was developed and validated that is generally regarded as being selective for measurement of CYP1A2 activity (Tassaneeyakul et al, 1993). The K m was determined at 47.0 Ϯ 1.9 M for pooled HLM and 16.7 Ϯ 0.9 M for rCYP1A2 (Table 7 Brosen et al, 1993;Tassaneeyakul et al, 1993;Bourrie et al, 1996;Schmider et al, 1996;Von Moltke et al, 1996a;Rodrigues et al, 1997;Agundez et al, 1998;Eagling et al, 1998;Kobayashi et al, 1999;Belle et al, 2000;Li et al, 2003) (Fig. 4).…”

Section: Resultsmentioning

confidence: 99%

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Validated Assays for Human Cytochrome P450 Activities

Walsky

Obach²

2004

Drug Metabolism and Disposition

469

380

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ABSTRACT:The measurement of the effect of new chemical entities on human cytochrome P450 marker activities using in vitro experimentation represents an important experimental approach in drug development. In vitro drug interaction data can be used in guiding the design of clinical drug interaction studies, or, when no effect is observed in vitro, the data can be used in place of an in vivo study to claim that no interaction will occur in vivo. To make such a claim, it must be assured that the in vitro experiments are performed with absolute confidence in the methods used and data obtained. To meet this need, 12 semiautomated assays for human P450 marker substrate activities have been developed and validated using approaches described in the GLP (good laboratory practices) as per the code of U.S. Federal Regulations. The assays that were validated are: phenacetin O-deethylase (CYP1A2), coumarin 7-hydroxylase (CYP2A6), bupropion hydroxylase (CYP2B6), amodiaquine N-deethylase (CYP2C8), diclofenac 4-hydroxylase and tolbutamide methylhydroxylase (CYP2C9), (S)-mephenytoin 4-hydroxylase (CYP2C19), dextromethorphan O-demethylase (CYP2D6), chlorzoxazone 6-hydroxylase (CYP2E1), felodipine dehydrogenase, testosterone 6␤-hydroxylase, and midazolam 1-hydroxylase (CYP3A4 and CYP3A5). High-pressure liquid chromatography-tandem mass spectrometry, using stable isotope-labeled internal standards, has been applied as the analytical method. This analytical approach, through its high sensitivity and selectivity, has permitted the use of very low incubation concentrations of microsomal protein (0.01-0.2 mg/ml). Analytical assay accuracy and precision values were excellent. Enzyme kinetic and inhibition parameters obtained using these methods demonstrated high precision and were within the range of values previously reported in the scientific literature. These methods should prove useful in the routine assessments of the potential for new drug candidates to elicit pharmacokinetic drug interactions via inhibition of cytochrome P450 activities.Drug-drug interactions are of great interest to scientists involved in drug research, regulatory authorities who are responsible for public safety, physicians, and their patients. Since "polypharmacy," or the practice of simultaneous prescription of more than one drug to treat one or more conditions in a single patient, has become a more common practice, drug interactions have been cited as one of the major reasons for hospitalization and even death (Lazarou et al., 1998). Thus, a great deal of effort is expended by researchers engaged in new drug research in avoiding the development of compounds that will cause drug-drug interactions.The most common mechanism underlying drug-drug interactions is the inhibition of cytochrome P450 activities. Several drugs in common use cause large increases in exposure to other drugs. Examples include ketoconazole, itraconazole, erythromycin, clarithromycin, diltiazem, and nefazodone (CYP3A); quinidine, paroxetine, and terbinafine (CYP2D6); ticlopidine (CYP2C19); ...

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Section: Resultssupporting

confidence: 59%

Section: Resultsmentioning

confidence: 99%

Validated Assays for Human Cytochrome P450 Activities

Walsky

Obach²

2004

Drug Metabolism and Disposition

469

380

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“…Nissbrandt et al (2001) have also shown that inhibitors of CYP2E1 affect dopaminergic neurotransmission in the substantia nigra, possibly by participating in the dopamine metabolism. This modulation of enzyme activity rather than the enzyme expression by endogenous substrates has been shown for CYP1A2 indicating that the local activity of brain CYP1A2 might be susceptible to the local regulatory mechanisms (Agundez et al, 1998).…”

Section: Discussionmentioning

confidence: 60%

Differences in sensitivity of cultured rat brain neuronal and glial cytochrome P450 2E1 to ethanol

et al. 2006

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“…Because many endogenous compounds are substrates of P450s, they may inhibit drug metabolism catalyzed by P450s. Previous studies reported that human CYP1A2 (Agúndez et al, 1998), CYP2C9 (Gervasini et al, 2001), CYP2D6 (Martínez et al, 1997), and CYP3A (Martínez et al, 2000) activities were inhibited by neurotransmitters and their precursors. The inhibition would be of particular importance, since these P450s are expressed in brain and are involved in the metabolism of psychoactive drugs or associated with Parkinson's disease.…”

mentioning

confidence: 95%

Inhibitory Effects of Neurotransmitters and Steroids on Human CYP2A6

Higashi

Nakajima²,

Katoh³

et al. 2007

Drug Metabolism and Disposition

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ABSTRACT:Human CYP2A6 catalyzes the metabolism of nicotine, cotinine, and coumarin as well as some pharmaceutical drugs. CYP2A6 is highly expressed in liver and, also, in brain and steroid-related tissues. In this study, we investigated the inhibitory effects of neurotransmitters and steroid hormones on CYP2A6 activity. We found that coumarin 7-hydroxylation and cotinine 3-hydroxylation by recombinant CYP2A6 expressed in baculovirus-infected insect cells were competitively inhibited by tryptamine (both Thus, we found that some neurotransmitters inhibit CYP2A6 activity, being related with inter-and intraindividual differences in CYP2A6-dependent metabolism. The inhibitory effects of steroid hormones on aldehyde oxidase may also contribute to interindividual differences in nicotine metabolism.

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Modulation of CYP1A2 enzyme activity by indoleamines

Cited by 15 publications

References 0 publications

Validated Assays for Human Cytochrome P450 Activities

Validated Assays for Human Cytochrome P450 Activities

Differences in sensitivity of cultured rat brain neuronal and glial cytochrome P450 2E1 to ethanol

Inhibitory Effects of Neurotransmitters and Steroids on Human CYP2A6

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