Details of Drug Interaction | MecDDI

Drug General Information (ID: DDIPQL9S28)
Drug Name			Brimonidine (topical)		Drug Info		Safinamide		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Ophthalmic Glaucoma Agents				Dopaminergic Antiparkinsonism Agents
Structure

Mechanism of Brimonidine (topical)-Safinamide Interaction (Severity Level: Moderate)
Additive hypertensive effects Click to Show/Hide Mechanism Graph

Drug Name		Brimonidine (topical)				Safinamide
Mechanism		Hypertensive effects Alpha-1 adrenergic receptor Agonist				Hypertensive effects Monoamine oxidase non-selective Inhibitor
Key Mechanism Factor 1
		Factor Name		Adrenergic receptor alpha-1				Structure Sequence
		Protein Family		G-protein coupled receptor 1 family
		Protein Function		This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine(PE)-stimulated ERK signaling in cardiac myocytes. Click to Show/Hide
Key Mechanism Factor 2
		Factor Name		Monoamine oxidase				Structure Sequence
		Protein Family		Flavin monoamine oxidase family
		Protein Function		Catalyzes the oxidative deamination of primary and some secondary amine such as neurotransmitters, with concomitant reduction of oxygen to hydrogen peroxide and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues (PubMed:20493079, PubMed:8316221, PubMed:18391214, PubMed:24169519). Preferentially oxidizes serotonin (PubMed:20493079, PubMed:24169519). Also catalyzes the oxidative deamination of kynuramine to 3-(2-aminophenyl)-3-oxopropanal that can spontaneously condense to 4-hydroxyquinoline (By similarity). Click to Show/Hide
Mechanism Description		Additive hypertensive effects by the combination of Brimonidine (topical) and Safinamide

Recommended Action
Management		Patients receiving brimonidine in combination with MAOIs should be made aware of the potential for increased adverse effects, and counseled to avoid activities requiring mental alertness until they know how these agents affect them. Patients should also avoid rising abruptly from a sitting or recumbent position and notify their physician if they experience orthostasis or tachycardia. Blood pressure should be monitored closely.

References
1	Coleman AL, Robin AL, Pollack IP, Rudikoff MT, Enger C, Mayer PR "Cardiovascular and intraocular pressure effects and plasma concentrations of apraclonidine." Arch Ophthalmol 108 (1990): 1264-7. [PMID: 2205182]
2	Kronig MH, Roose SP, Walsh BT, Woodring S, Glassman AH "Blood pressure effects of phenelzine." J Clin Psychopharmacol 3 (1983): 307-10. [PMID: 6630590]
3	Schulz R, Antonin KH, Hoffmann E, et al "Tyramine kinetics and pressor sensitivity during monoamine oxidase inhibition by selegiline." Clin Pharmacol Ther 46 (1989): 528-36. [PMID: 2510962]