Phenazopyridine Hydrochloride/Sulfisoxazole

The effects were examined of four metabolites of the anticancer agent, procarbazine (N-isopropyl-α-(2−methyl hydrazino)-p-toluamide hydrochloride) on semicarbazide-sensitive amine oxidase (SSAO) and monoamine oxidase-A and -B (MAO-A and -B) activities in rat brown adipose tissue and liver homogenates, respectively. Azoprocarbazine (AZO) and monomethylhydrazine (MMH) inhibited selectively the deamination of benzylamine by SSAO, when compared with their effects on MAO activities. The IC50 values against SSAO, of 32·7 Nm (AZO) and 7·0 Nm (MMH), were more than three orders of magnitude lower than those exhibited against MAO. Neither isomer of azoxyprocarbazine was an effective inhibitor of rat amine oxidase activities. The inhibition of SSAO by AZO was reversed very slowly by dialysis, in contrast to results seen for MMH. The non-competitive kinetics of MMH and the ability of B24, a rapidly reversible SSAO inhibitor, to protect SSAO against inhibition by MMH are consistent with the view that this compound binds to the enzyme cofactor at, or near, the active site.

The TXA2 receptor antagonist properties of SQ 27,427 (a novel oxabicyclo[2.2.1]heptane derivative) were studied in vivo in the anesthetized guinea pig where changes in pulmonary resistance, dynamic compliance, and mean arterial blood pressure were measured. Both the bronchoconstrictor and pressor responses to arachidonic acid (AA) and to the stable TXA2 mimic 9,11-azoPGH2 (AZO) were taken as indices of in vivo TXA2 receptor activation. The administration of SQ 27,427 (0.1-1.0 mg/kg i.v., and 10.0 mg/kg p.o.) caused dose-related inhibitions of both AA- and AZO-induced bronchoconstriction. Relative specificity of this antagonism was evidenced by the failure of SQ 27,427 (1.0 mg/kg i.v.) to inhibit histamine-induced bronchoconstriction. In the same experiments the pressor response to AA was reversed to a depressor response by SQ 27,427. This reversal was abolished by indomethacin. The pressor response to AZO was antagonized by SQ 27,427, but not by indomethacin. The reversal of the pressor response to AA by SQ 27,427 may be due to the unmasking of the depressor effect of a cyclooxygenase product, i.e., prostacyclin. It is concluded that SQ 27,427 is a relatively specific TXA2 receptor antagonist in vivo in the guinea pig.