Selective inhibitors of monoamine oxidase. 3. Structure-activity relationship of tricyclics bearing imidazoline, oxadiazole, or tetrazole groups.

Inhibition of monoamine oxidase A (MAO A) is believed to cause antidepressant and possibly antianxiety effects. The previous paper had developed structure-activity relationships (SAR) for in vitro MAO A inhibition by tricyclic N-arylamides. It is shown in this paper that the same in vitro SAR can be carried over to tricyclics whose potentially toxic amide function is replaced by an appropriately substituted imidazoline, a 1,2,4- or 1,3,4-oxadiazole, or an alkylated tetrazole moiety. Dialysis of the inhibitor from the enzyme was used as a measure of reversibility which correlates with a low ability to cause a blood pressure rise with ingested tyramine ("cheese effect").

Modification of the haemoglobin oxygen dissociation curve in whole blood by a compound with dual action.

2-Ethoxy-6-(5-tetrazolyl)xanthone reduces the oxygen affinity of blood by two mechanisms; firstly, by a direct effect on the haemoglobin molecule and secondly by maintaining levels of 2,3-diphosphoglycerate (DPG) in stored blood. This compound thus has potential as a blood storage additive which will improve the oxygen delivery of stored blood.

Doxantrazole, an antiallergic agent orally effective in man.

In-vivo studies have demonstrated antiallergic properties in doxantrazole when given orally to rats. These properties were confirmed in work with in-vitro preparations. No significant animal toxicity has been detected. 200 mg. given by mouth inhibited the immediate-type asthmatic response in volunteer patients challenged with specific antigen.