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The He1 photoelectron (PE) spectra of imidazole, I-methylimidazolc. 2-methylimidazole. and 4(5)-methylimidazole are rcported. The electronic structure of imidazole is discussed on the basis of high resolution spectra and molecular orbital (MO) calculations. Methyl substitution in imidazole. apart from a nearly constant destabilization of low-energy ionizations. causes a negligible change in the shape of its PE spectrum. Probably this was the reason why there was no indication for the presence of two tautomers in the PE spectrum of 4(5)-methylimidazole.

1. Ranitidine interacts with liver microsomes from rats pretreated with different inducers of cytochrome P-450 to produce substrate difference optical spectra with a peak at 426-429 nm and a trough at 390-400 nm. 2. Cytochrome P-450 reduced with dithionite in the presence of ranitidine produced substrate difference spectra with a peak at 447 nm. 3. Ks values for the interaction of ranitidine with cytochrome P-450 (not reduced), calculated from double reciprocal plots, were in the range 1.4-2.8 mM. 4. The O-dealkylation of 7-ethoxycoumarin and of p-nitroanisole was inhibited by the presence of ranitidine and the inhibition was of a mixed type. Kii and Kis values were: for inhibition of 7-ethoxycoumarin dealkylation, 0.8 to 9 mM, and 0.16 to 0.67 mM, respectively; for inhibition of p-nitroanisole dealkylation, 5.8 to 13.7 mM, and 1 to 4.5 mM, respectively. 5. The I50 values for 7-ethoxycoumarin dealkylation was 1.8 mM and for p-nitroanisole dealkylation about 7.2 mM (microsomes from phenobarbital-pretreated rats). 6. The e.p.r. spectra of cytochrome P-450 from phenobarbital-pretreated rats, in the presence of ranitidine, reveal two types of interaction depending on the ranitidine concentration. At lower concentrations of ranitidine, a ligand exchange reaction with an oxygen atom is indicated, and at higher concentrations are with nitrogenous or thioether ligand of ranitidine.

Cimetidine and ranitidine interact with microsomes from human and pig liver and with purified cytochrome P-450 in the ligand-type manner. The affinity for cimetidine is about 10 times as high as that for ranitidine. Accordingly amplitudes of the specta are much higher for cimetidine. These results are in accordance with those obtained earlier with rat liver microsomes. The inhibitory potency of either compound with regard to dealkylation of 7-ethoxycoumarin appears to be less in the human preparation.