Details of Drug Interaction | MecDDI

Drug General Information (ID: DDIQ3KWUH9)
Drug Name			Chlorothiazide		Drug Info		Safinamide		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Antihypertensive Agents				Dopaminergic Antiparkinsonism Agents
Structure

Mechanism of Chlorothiazide-Safinamide Interaction (Severity Level: Moderate)
Additive hypotensive effects Click to Show/Hide Mechanism Graph

Drug Name		Chlorothiazide				Safinamide
Mechanism		Hypotensive effects Carbonic anhydrase II Inhibitor				Hypotensive effects Monoamine oxidase-B selective Inhibitor
Key Mechanism Factor 1
		Factor Name		Carbonic anhydrase II				× Structure Sequence MSHHWGYGKHNGPEHWHKDFPIAKGERQSPVDIDTHTAKYDPSLKPLSVSYDQATSLRILNNGHAFNVEFDDSQDKAVLKGGPLDGTYRLIQFHFHWGSLDGQGSEHTVDKKKYAAELHLVHWNTKYGDFGKAVQQPDGLAVLGIFLKVGSAKPGLQKVVDVLDSIKTKGKSADFTNFDPRGLLPESLDYWTYPGSLTTPPLLECVTWIVLKEPISVSSEQVLKFRKLNFNGEGEPEELMVDNWRPAQPLKNRQIKASFK
		Gene Name		CA2
		Uniprot ID		CAH2_HUMAN
		KEGG Pathway		hsa:760
		Protein Family		Alpha-carbonic anhydrase family
		Protein Function		Catalyzes the reversible hydration of carbon dioxide (PubMed:1909891, PubMed:1910042, PubMed:1336460, PubMed:8485129, PubMed:8399159, PubMed:8218160, PubMed:8262987, PubMed:8451242, PubMed:7901850, PubMed:7761440, PubMed:8639494, PubMed:9265618, PubMed:17330962, PubMed:9398308, PubMed:11327835, PubMed:12056894, PubMed:17346964, PubMed:12171926, PubMed:15453828, PubMed:16214338, PubMed:15865431, PubMed:16106378, PubMed:15300855, PubMed:15667203, PubMed:18942852, PubMed:11831900, PubMed:17251017). Can also hydrate cyanamide to urea (PubMed:10550681, PubMed:11015219). Stimulates the chloride-bicarbonate exchange activity of SLC26A6 (PubMed:15990874). Essential for bone resorption and osteoclast differentiation (PubMed:15300855). Involved in the regulation of fluid secretion into the anterior chamber of the eye. Contributes to intracellular pH regulation in the duodenal upper villous epithelium during proton-coupled peptide absorption. Click to Show/Hide
Key Mechanism Factor 2
		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
Mechanism Description		Additive hypotensive effects by the combination of Chlorothiazide and Safinamide

Recommended Action
Management		Caution is advised during coadministration of MAOIs and other medications with hypotensive effects, especially during the first few weeks of treatment. Close monitoring for development of hypotension is recommended. Ambulatory patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia.

References
1	Ban TA "Drug interactions with psychoactive drugs." Dis Nerv Syst 36 (1975): 164-6. [PMID: 1116424]
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	Goldberg LI "Monoamine oxidase inhibitors: adverse reactions and possible mechanisms." JAMA 190 (1964): 456-62. [PMID: 14197995]
4	Golwyn DH, Sevlie CP "Monoamine oxidase inhibitor hypertensive crisis headache and orthostatic hypotension." J Clin Psychopharmacol 13 (1993): 77-8. [PMID: 8486823]
5	Kronig MH, Roose SP, Walsh BT, Woodring S, Glassman AH "Blood pressure effects of phenelzine." J Clin Psychopharmacol 3 (1983): 307-10. [PMID: 6630590]
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. Marplan (isocarboxazid) Roche Laboratories, Nutley, NJ.
8	Product Information. Matulane (procarbazine). Roche Laboratories, Nutley, NJ.
9	Product Information. Nardil (phenelzine). Parke-Dvis, Morris Plains, NJ.
10	Product Information. Parnate (tranylcypromine). SmithKline Beecham, Philadelphia, PA.
11	Product Information. Xatral (alfuzosin). Sanofi-Synthelabo Canada Inc, Markham, ON.
12	Reggev A, Vollhardt BR "Bradycardia induced by an interaction between phenelzine and beta blockers." Psychosomatics 30 (1992): 106-8. [PMID: 2913594]
13	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]