Details of Drug Interaction | MecDDI

Drug General Information (ID: DDITEVDCOW)
Drug Name			Amitriptyline		Drug Info		Lorcaserin		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Analgesics				Anorexiants
Structure

Mechanism of Amitriptyline-Lorcaserin Interaction (Severity Level: Major)
Additive serotonergic effects Click to Show/Hide Mechanism Graph

Drug Name		Amitriptyline				Lorcaserin
Mechanism		Serotonergic effects Serotonin transporter Inhibitor				Serotonergic effects 5-HT 2 receptor Agonist
Key Mechanism Factor 1
		Factor Name		Serotonin transporter				× Structure Sequence METTPLNSQKQLSACEDGEDCQENGVLQKVVPTPGDKVESGQISNGYSAVPSPGAGDDTRHSIPATTTTLVAELHQGERETWGKKVDFLLSVIGYAVDLGNVWRFPYICYQNGGGAFLLPYTIMAIFGGIPLFYMELALGQYHRNGCISIWRKICPIFKGIGYAICIIAFYIASYYNTIMAWALYYLISSFTDQLPWTSCKNSWNTGNCTNYFSEDNITWTLHSTSPAEEFYTRHVLQIHRSKGLQDLGGISWQLALCIMLIFTVIYFSIWKGVKTSGKVVWVTATFPYIILSVLLVRGATLPGAWRGVLFYLKPNWQKLLETGVWIDAAAQIFFSLGPGFGVLLAFASYNKFNNNCYQDALVTSVVNCMTSFVSGFVIFTVLGYMAEMRNEDVSEVAKDAGPSLLFITYAEAIANMPASTFFAIIFFLMLITLGLDSTFAGLEGVITAVLDEFPHVWAKRRERFVLAVVITCFFGSLVTLTFGGAYVVKLLEEYATGPAVLTVALIEAVAVSWFYGITQFCRDVKEMLGFSPGWFWRICWVAISPLFLLFIICSFLMSPPQLRLFQYNYPYWSIILGYCIGTSSFICIPTYIAYRLIITPGTFKERIIKSITPETPTEIPCGDIRLNAV
		Gene Name		SLC6A4
		Uniprot ID		SC6A4_HUMAN
		KEGG Pathway		hsa:6532
		Protein Family		Sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family
		Protein Function		Serotonin transporter whose primary function in the central nervous system involves the regulation of serotonergic signaling via transport of serotonin molecules from the synaptic cleft back into the pre-synaptic terminal for re-utilization. Plays a key role in mediating regulation of the availability of serotonin to other receptors of serotonergic systems. Terminates the action of serotonin and recycles it in a sodium-dependent manner. Click to Show/Hide
Key Mechanism Factor 2
		Factor Name		5-HT 2 receptor				Structure Sequence
		Protein Family		G-protein coupled receptor 1 family
		Protein Function		G-protein coupled receptor for 5-hydroxytryptamine (serotonin) (PubMed:1330647, PubMed:18703043, PubMed:19057895). Also functions as a receptor for various drugs and psychoactive substances, including mescaline, psilocybin, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and lysergic acid diethylamide (LSD) (PubMed:28129538). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors (PubMed:28129538). Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways (PubMed:28129538). Signaling activates phospholipase C and a phosphatidylinositol-calcium second messenger system that modulates the activity of phosphatidylinositol 3-kinase and promotes the release of Ca(2+) ions from intracellular stores (PubMed:18703043, PubMed:28129538). Affects neural activity, perception, cognition and mood (PubMed:18297054). Plays a role in the regulation of behavior, including responses to anxiogenic situations and psychoactive substances. Plays a role in intestinal smooth muscle contraction, and may play a role in arterial vasoconstriction. Click to Show/Hide
Mechanism Description		Additive serotonergic effects by the combination of Amitriptyline and Lorcaserin

Recommended Action
Management		Caution is advised if lorcaserin must be used in combination with other agents that affect the serotonergic neurotransmitter system. Patients should be closely monitored for symptoms of the serotonin syndrome, which may include mental status changes such as irritability, altered consciousness, confusion, hallucinations, and coma autonomic dysfunction such as tachycardia, hyperthermia, diaphoresis, shivering, blood pressure lability, and mydriasis neuromuscular abnormalities such as hyperreflexia, myoclonus, tremor, rigidity, and ataxia and gastrointestinal symptoms such as abdominal cramping, nausea, vomiting, and diarrhea. Particular caution is advised when initiating or increasing the dosages of these agents. The potential risk for serotonin syndrome should be considered even when administering serotonergic agents sequentially, as some agents may demonstrate a prolonged elimination half-life. For example, a 5-week washout period is typically recommended following use of fluoxetine and 2 weeks following use of MAOIs before administering another serotonergic agent. If serotonin syndrome develops or is suspected during the course of therapy, all serotonergic agents should be discontinued immediately and supportive care rendered as necessary.

References
1	Product Information. Belviq (lorcaserin). Eisai Inc, Teaneck, NJ.