Blood pressure effects of monoamine oxidase inhibitors in response to orally administered tyramine in the rat

Abstract

Carroll, M., and 0. Beek: Blood pressure effects of monoamine oxidase inhibitors in response to orally administered tyramine in the rat. Drug Dev. Res. 2321 5-21 8, 1992.The reversible monoamine oxidase-A inhibitors BW 1370U87, BW 61 6U76, brofaromine, and moclobemide, and the irreversible nonselective monoamine oxidase inhibitor phenelzine were compared for potentiation of the pressor response to oral tyramine. Conscious rats were pretreated with doses of the monoamine oxidase inhibitors sufficient to produce 80% inhibition of brain monoamine oxidase, and then were challenged with orally administered tyramine. Blood pressure was monitored prior to and after tyramine, and peak pressor responses were compared. At a dose of 15 mg/kg tyramine, the pressor response of BW 1370U87 was statistically similar to the vehicle control response. BW 6161176, brofaromine, and moclobemide elicited mild tyramine pressor effects, whereas phenelzine resulted in a marked elevation of blood pressure. Higher doses of tyramine elicited blood pressure elevations from all of the monoamine oxidase inhibitors.

Selective Inhibitors of Monoamine Oxidase (MAO). 5. 1-Substituted Phenoxathiin Inhibitors Containing No Nitrogen That Inhibit MAO A by Binding It to a Hydrophobic Site

“…The monomethyl sulfone 3 was ruled out since it was partly irreversibly bound to MAO A, i.e., not completely dissociated from the enzyme in 24 h of dialysis. This irreversibility has been shown to be associated with tyramine-induced blood pressure rise, and indeed, after pretreatment with this compound, the blood pressure of tyramine-fed rats rose to 36% of that induced by phenelzine pretreatment under our standard test conditions . The 3-bromo sulfone 75 , while potent in vitro, showed no activity in rat brain MAO 3 h after oral administration at 20 mg/kg, the ED 50 cutoff selected.…”

“…This irreversibility has been shown to be associated with tyramine-induced blood pressure rise, 1 and indeed, after pretreatment with this compound, the blood pressure of tyramine-fed rats rose to 36% of that induced by phenelzine pretreatment under our standard test conditions. 10 The 3-bromo sulfone 75, while potent in vitro, showed no activity in rat brain MAO 3 h after oral administration at 20 mg/ kg, the ED 50 cutoff selected. The 1-ethylphenoxathiin dioxide 13 was preferred to the 1-vinyl ( 22), the 1-trifluoromethyl (27), and the 1-iodo (76) phenoxathiin dioxides on pharmacokinetic and other grounds, since all showed low acute toxicity, all showed negligible MAO B inhibition, and none caused significant tyramineinduced blood rise above vehicle control values in rats given 15 mg/kg tyramine orally after 80% inhibition of brain MAO had been established by the required dosage of inhibitor.…”

Biochemical and pharmacologic properties of 2614W94, a reversible, competitive inhibitor of monoamine oxidase-A

“…The interactions of MAO inhibitors with a threshold dose of orally administered tyramine were evaluated in conscious normotensive male rats (Sprague-Dawley, Charles River) by using a method described by Carroll and Beek [1992].…”