Details of Drug Interaction | MecDDI

Drug General Information (ID: DDIYR5CZUT)
Drug Name			Selegiline		Drug Info		Guanethidine		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Dopaminergic Antiparkinsonism Agents/Mao Inhibitors				Antihypertensive Agents
Structure

Mechanism of Selegiline-Guanethidine Interaction (Severity Level: Moderate)
Antagonize the effect of antihypertensive agents Click to Show/Hide Mechanism Graph

Drug Name		Selegiline				Guanethidine
Mechanism		Hypertensive effects Monoamine oxidase-B selective Inhibitor				Antihypertensive agent Noradrenaline transporter Inducer
Key Mechanism Factor 1
		Factor Name		Monoamine oxidase type B				× Structure Sequence MSNKCDVVVVGGGISGMAAAKLLHDSGLNVVVLEARDRVGGRTYTLRNQKVKYVDLGGSYVGPTQNRILRLAKELGLETYKVNEVERLIHHVKGKSYPFRGPFPPVWNPITYLDHNNFWRTMDDMGREIPSDAPWKAPLAEEWDNMTMKELLDKLCWTESAKQLATLFVNLCVTAETHEVSALWFLWYVKQCGGTTRIISTTNGGQERKFVGGSGQVSERIMDLLGDRVKLERPVIYIDQTRENVLVETLNHEMYEAKYVISAIPPTLGMKIHFNPPLPMMRNQMITRVPLGSVIKCIVYYKEPFWRKKDYCGTMIIDGEEAPVAYTLDDTKPEGNYAAIMGFILAHKARKLARLTKEERLKKLCELYAKVLGSLEALEPVHYEEKNWCEEQYSGGCYTTYFPPGILTQYGRVLRQPVDRIYFAGTETATHWSGYMEGAVEAGERAAREILHAMGKIPEDEIWQSEPESVDVPAQPITTTFLERHLPSVPGLLRLIGLTTIFSATALGFLAHKRGLLVRV
		Gene Name		MAOB
		Uniprot ID		AOFB_HUMAN
		KEGG Pathway		hsa:4129
		Protein Family		Flavin monoamine oxidase family
		Protein Function		Catalyzes the oxidative deamination of primary and some secondary amines such as neurotransmitters, and exogenous amines including the tertiary amine, neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), with concomitant reduction of oxygen to hydrogen peroxide and participates in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues (PubMed:11134050, PubMed:8665924, PubMed:8316221, PubMed:11049757, PubMed:20493079). Preferentially degrades benzylamine and phenylethylamine (PubMed:11134050, PubMed:8665924, PubMed:8316221, PubMed:11049757, PubMed:20493079). Click to Show/Hide
Key Mechanism Factor 2
		Factor Name		Norepinephrine transporter				× Structure Sequence MLLARMNPQVQPENNGADTGPEQPLRARKTAELLVVKERNGVQCLLAPRDGDAQPRETWGKKIDFLLSVVGFAVDLANVWRFPYLCYKNGGGAFLIPYTLFLIIAGMPLFYMELALGQYNREGAATVWKICPFFKGVGYAVILIALYVGFYYNVIIAWSLYYLFSSFTLNLPWTDCGHTWNSPNCTDPKLLNGSVLGNHTKYSKYKFTPAAEFYERGVLHLHESSGIHDIGLPQWQLLLCLMVVVIVLYFSLWKGVKTSGKVVWITATLPYFVLFVLLVHGVTLPGASNGINAYLHIDFYRLKEATVWIDAATQIFFSLGAGFGVLIAFASYNKFDNNCYRDALLTSSINCITSFVSGFAIFSILGYMAHEHKVNIEDVATEGAGLVFILYPEAISTLSGSTFWAVVFFVMLLALGLDSSMGGMEAVITGLADDFQVLKRHRKLFTFGVTFSTFLLALFCITKGGIYVLTLLDTFAAGTSILFAVLMEAIGVSWFYGVDRFSNDIQQMMGFRPGLYWRLCWKFVSPAFLLFVVVVSIINFKPLTYDDYIFPPWANWVGWGIALSSMVLVPIYVIYKFLSTQGSLWERLAYGITPENEHHLVAQRDIRQFQLQHWLAI
		Gene Name		SLC6A2
		Uniprot ID		SC6A2_HUMAN
		KEGG Pathway		hsa:6530
		Protein Family		Sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family
		Protein Function		Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals. Click to Show/Hide
Mechanism Description		Antagonize the effect of Guanethidine when combined with Selegiline

Recommended Action
Management		While clinical data are lacking, guanadrel and guanethidine should preferably not be used with MAOIs or other agents that possess MAOI activity (e.g., furazolidone, linezolid, methylene blue, procarbazine). The manufacturer of phenelzine considers the combination contraindicated. At least 7 to 14 days should elapse between discontinuation of MAOI therapy and initiation of treatment with guanadrel or guanethidine. If they have been used together, clinicians should be aware that significant hypotension may occur following withdrawal of MAOI therapy.

References
1	Darcy PF, Griffin JP "Interactions with drugs used in the treatment of depressive illness." Adverse Drug React Toxicol Rev 14 (1995): 211-31. [PMID: 8845455]
2	De Vita VT, Hahn MA, Oliverio VT "Monoamine oxidase inhibition by a new carcinostatic agent, n-isopropyl-a-(2-methylhydrazino)-p-toluamide (MIH). (30590)." Proc Soc Exp Biol Med 120 (1965): 561-5. [PMID: 4379192]
3	Gulati OD, Dave BT, Gokhale SD, Shah KM "Antagonism of adrenergic neuron blockade in hypertensive subjects." Clin Pharmacol Ther 7 (1966): 510-4. [PMID: 5939974]
4	Iversen LL "Inhibition of noradrenaline uptake by drugs." J Pharm Pharmacol 17 (1965): 62-4. [PMID: 14285701]
5	Lee CH, Strosberg AM, Warren LA "The importance of catecholamine uptake in the reversal of guenethidine blockade of adrenergic neurons." Res Commun Chem Pathol Pharmacol 30 (1980): 3-14. [PMID: 7433767]
6	Pettinger WA, Soyangco FG, Oates JA "Inhibition of monoamine oxidase in man by furazolidone." Clin Pharmacol Ther 9 (1968): 442-7. [PMID: 5655478]
7	Product Information. Nardil (phenelzine). Parke-Dvis, Morris Plains, NJ.
8	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]