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Biomedical subjects

B Testa

Publications and source records attributed to B Testa.

At least 109 records · Page 6Linked to original sources
PubMed1976

A reappraisal of the stereoselective metabolism of nicotine to nicotine-1'-N-oxide.

1. The cis and trans 1'-N-oxide metabolites of (2'R)-(+)-nicotine have the absolute configuration (1'S; 2'R) and (1'R; 2'R), respectively, and not the reverse as previously published. 2. Reinterpretation of metabolic data in the light of this reassignment reveals that N-oxidation of nicotine leads preferentially to the (1'R)-N-oxide, with little dependence on the configuration of the 2'-centre. 3. It is proposed that (2'S)-(-)-nicotine and (2'R)-(+)-nicotine bind to the same enzymic site by two distinct modes of binding; each of these modes involves the more basic centre (in this case the pyrrolidine ring) as the governing binding moiety.

Animals↗
PubMedDate not supplied

Isomerisation and urinary excretion of proxibarbal and valofan in man; a preliminary study.

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↗