Details of Drug Interaction | MecDDI

Drug General Information (ID: DDIN2K7QYG)
Drug Name			Zolmitriptan		Drug Info		Lasmiditan		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Antimigraine Agents				Antimigraine Agents
Structure

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

Drug Name		Zolmitriptan				Lasmiditan
Mechanism		Serotonergic effects 5-HT 1 receptor Agonist				Serotonergic effects 5-HT 1F receptor Agonist
Key Mechanism Factor 1
		Factor Name		5-HT 1 receptor				Structure Sequence
		Protein Family		G-protein coupled receptor 1 family
		Protein Function		G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling inhibits adenylate cyclase activity and activates a phosphatidylinositol-calcium second messenger system that regulates the release of Ca(2+) ions from intracellular stores. Plays a role in the regulation of 5-hydroxytryptamine release and in the regulation of dopamine and 5-hydroxytryptamine metabolism. Plays a role in the regulation of dopamine and 5-hydroxytryptamine levels in the brain, and thereby affects neural activity, mood and behavior. Plays a role in the response to anxiogenic stimuli. Click to Show/Hide
Key Mechanism Factor 2
		Factor Name		5-hydroxytryptamine receptor 1F				× Structure Sequence MDFLNSSDQNLTSEELLNRMPSKILVSLTLSGLALMTTTINSLVIAAIIVTRKLHHPANYLICSLAVTDFLVAVLVMPFSIVYIVRESWIMGQVVCDIWLSVDITCCTCSILHLSAIALDRYRAITDAVEYARKRTPKHAGIMITIVWIISVFISMPPLFWRHQGTSRDDECIIKHDHIVSTIYSTFGAFYIPLALILILYYKIYRAAKTLYHKRQASRIAKEEVNGQVLLESGEKSTKSVSTSYVLEKSLSDPSTDFDKIHSTVRSLRSEFKHEKSWRRQKISGTRERKAATTLGLILGAFVICWLPFFVKELVVNVCDKCKISEEMSNFLAWLGYLNSLINPLIYTIFNEDFKKAFQKLVRCRC
		Gene Name		HTR1F
		Uniprot ID		5HT1F_HUMAN
		KEGG Pathway		hsa:3355
		Protein Family		G-protein coupled receptor 1 family
		Protein Function		G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various alkaloids and psychoactive substances. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase activity. Click to Show/Hide
Mechanism Description		Additive serotonergic effects by the combination of Zolmitriptan and Lasmiditan

Recommended Action
Management		Caution is advised during coadministration of lasmiditan and agents that increase serotonin. Patients should be closely monitored for symptoms of the serotonin syndrome during treatment. Extra caution is advised when 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.

References
1	Product Information. Fycompa (perampanel). Eisai Inc, Teaneck, NJ.
2	Product Information. Reyvow (lasmiditan). Lilly, Eli and Company, Indianapolis, IN.
3	Warrington SJ, Ankier SI, Turner P "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology 15 (1986): 31-7. [PMID: 3725002]