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  • Title: The action of nitrophenols on the pulmonary ventilation of rats.
    Author: GRANT CM.
    Journal: Br J Pharmacol Chemother; 1959 Sep; 14(3):401-3. PubMed ID: 13828953.
    Abstract:
    The ventilatory effects of the three mononitrophenols and six dinitrophenols have been examined in anaesthetized rats. The minute volume of ventilation increased in all the test groups, the increase reaching the 99% significance level with seven compounds (P<0.01), the 95% level with 3-nitrophenol (P<0.05), and the 90% level with 3,5-dinitrophenol (P<0.10). The effects of 4-nitrophenol, 3,4-dinitrophenol, 3-nitrophenol, and 2,5-dinitrophenol, in increasing carbon dioxide output relative to oxygen consumption, are not explicable on the basis of simple hyperventilation, and are attributed to a metabolic effect at the cellular level. The potency of the nitrophenols in stimulating respiration is related to their structure, nitro groups being most effective in the ortho position and least effective in the meta position, and 2,4-dinitrophenol being the most powerful respiratory stimulant of the group. 2,6-Dinitrophenol does not conform to this generalization; one unique feature of its structure is indicated, as a possible explanation for the discrepancy. The gradation of potency of the nitrophenols (except 2,6-dinitrophenol) parallels the gradation of acidic properties in the group; the more strongly acid compounds stimulate respiration more powerfully. This is not a direct effect on blood pH, since the compounds were administered in neutral or slightly alkaline solution. Methaemoglobin formation was found to occur with 2,5-dinitrophenol, and to a smaller inconstant extent with three other compounds. Further work is suggested, to explore whether peripheral-acting ventilatory stimulation by 2,4-dinitrophenol is necessarily associated with peripheral metabolic enhancement, or whether the two effects can be dissociated.
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