Proxibarbal and valofan are tautomeric drugs which interconvert rapidly in solution. In the present study, the urinary excretion of these two drugs was investigated in two subjects after separate oral administration. In both cases, only proxibarbal was found in urine, while the excretion of valofan was negligible or non-detectable. More than half of a dose remains unaccounted for after proxibarbal administration, and more than three quarters after valofan administration. A simple chemical equilibrium of tautomerism as found in vitro is insufficient to account for the excretion kinetics of the two drugs in humans.

Adult↗

PubMedDate not supplied

Quantitative structure-metabolism relationship analyses of MAO-mediated toxication of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and analogues.

The 1-octanol/water partition coefficients of a number of toxic and nontoxic analogues of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were determined using centrifugal partition chromatography (CPC), a novel and effective technique for measuring lipophilicity, and found to be highly correlated with values calculated by a fragmental method. Some conformational properties of these compounds were also assessed by molecular mechanics calculations and 1H-NMR spectroscopy. A quantitative structure-metabolism relationship (QSMR) study of MPTP and analogues based on literature data was undertaken in order to determine the key features eliciting MAO-A and MAO-B reactivity and selectivity and influencing toxication. Multiple regression analysis (MRA) and comparative molecular field analysis (CoMFA) showed that MAO-B activity is nonlinearly (parabolically or bilinearly) correlated to the lipophilicity of MPTP analogues and influenced negatively by steric effects exerted by bulky substituents in the ortho position. With regard to MAO-A activity, while lipophilicity was shown to play no relevant role, electrostatic and steric fields led to a 3D-QSAR model with an acceptable predictive value (cross-validated r2 = 0.571). The results of this study bring evidence at a quantitative level that the MAO-B and MAO-A catalytic sites differ in their hydrophobic, steric, and stereoelectronic requirements.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMedDate not supplied

Structure-genotoxicity relationships of allylbenzenes and propenylbenzenes: a quantum chemical study.

Quantum mechanical calculations at the semiempirical level (AM1 method) were conducted for estragole (1), methyleugenol (2), safrole (3), alpha-asarone (4), beta-asarone (5), elemicin (6), allylbenzene (7), eugenol (8), trans-anethole (9), isosafrole (10), and myristicin (11), and the results compared with the known genotoxicity of 1-6 and the absence of genotoxicity of 7-11 (unscheduled DNA synthesis assay). The various compounds showed no significant differences in the relative stability of the radical species formed as intermediates in C-sp3 hydroxylation (delta HR(radical)) and in the corresponding enthalpy of activation (delta H++). In contrast, the carbonium ions of the genotoxic congeners 1-6 were shown to be comparatively more stable than those of the inactive compounds 7-11, with the exception of eugenol (8). The inactivity of this compound could be due to a very rapid stabilization of the carbonium ion by deprotonation to form a quinone methide, as suggested by quantum chemical calculations. The relative stability of the carbonium ion thus appears to be one of the key factors in the genotoxicity of allylbenzenes and propenylbenzenes.

Allylbenzene Derivatives↗

PubMedDate not supplied

Familial laryngeal abductor paralysis with presumed autosomal dominant inheritance.

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Female↗

PubMedDate not supplied

[Changes in serum levels of specific and total IgE in patients with allergic rhinopathy treated with H2 antagonists].

A study has been made of the effects of H2 antagonists in patients with perennial allergic rhinitis with sensitivity towards a single allergen: parietaria. During two years of observation. The patients underwent three cycles of treatment "a la demande". In 70% of the cases an improvement was observed in the symptomatology and a decrease in total serum IgE, while specific IgE remained unvaried. Subsequent treatments showed results overlapping the first, with further improvements.

Adolescent↗

PubMedDate not supplied