Details of Drug Interaction | MecDDI

Drug General Information (ID: DDI9LZ1IK8)
Drug Name			Trifluoperazine		Drug Info		Cyclandelate		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Antipsychotic Agents				Vasodilator Agents
Structure

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

Drug Name		Trifluoperazine				Cyclandelate
Mechanism		Hypotensive effects Calmodulin Inhibitor				Hypotensive effects Voltage-gated calcium channel Blocker
Key Mechanism Factor 1
		Factor Name		Calmodulin-1				× Structure Sequence MADQLTEEQIAEFKEAFSLFDKDGDGTITTKELGTVMRSLGQNPTEAELQDMINEVDADGNGTIDFPEFLTMMARKMKDTDSEEEIREAFRVFDKDGNGYISAAELRHVMTNLGEKLTDEEVDEMIREADIDGDGQVNYEEFVQMMTAK
		Gene Name		CALM1
		Uniprot ID		CALM1_HUMAN
		KEGG Pathway		hsa:801
		Protein Family		Calmodulin family
		Protein Function		Calmodulin mediates the control of a large number of enzymes, ion channels, aquaporins and other proteins through calcium-binding. Among the enzymes to be stimulated by the calmodulin-calcium complex are a number of protein kinases and phosphatases. Together with CCP110 and centrin, is involved in a genetic pathway that regulates the centrosome cycle and progression through cytokinesis (PubMed:16760425). Is a regulator of voltage-dependent L-type calcium channels (PubMed:31454269). Mediates calcium-dependent inactivation of CACNA1C (PubMed:26969752). Positively regulates calcium-activated potassium channel activity of KCNN2 (PubMed:27165696). Forms a potassium channel complex with KCNQ1 and regulates electrophysiological activity of the channel via calcium-binding (PubMed:25441029). Acts as a sensor to modulate the endoplasmic reticulum contacts with other organelles mediated by VMP1:ATP2A2 (PubMed:28890335). Click to Show/Hide
Key Mechanism Factor 2
		Factor Name		Voltage-dependent L-type calcium channel				Structure Sequence
		Protein Family		Calcium channel beta subunit family
		Protein Function		Regulatory subunit of L-type calcium channels (PubMed:1309651, PubMed:8107964, PubMed:15615847). Regulates the activity of L-type calcium channels that contain CACNA1A as pore-forming subunit (By similarity). Regulates the activity of L-type calcium channels that contain CACNA1C as pore-forming subunit and increases the presence of the channel complex at the cell membrane (PubMed:15615847). Required for functional expression L-type calcium channels that contain CACNA1D as pore-forming subunit (PubMed:1309651). Regulates the activity of L-type calcium channels that contain CACNA1B as pore-forming subunit (PubMed:8107964). Click to Show/Hide
Mechanism Description		Additive hypotensive effects by the combination of Trifluoperazine and Cyclandelate

Recommended Action
Management		Close clinical monitoring for development of hypotension is recommended if phenothiazines or neuroleptic agents are used in patients receiving antihypertensive medications or vasodilators. A lower starting dosage and slower titration of the phenothiazine or neuroleptic may be appropriate, especially in the elderly. 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. Patients should also avoid driving or operating hazardous machinery.

References
1	Aronowitz JS, Chakos MH, Safferman AZ, Lieberman JA "Syncope associated with the combination of clozapine and enalapril." J Clin Psychopharmacol 14 (1994): 429-30. [PMID: 7884028]
2	Fruncillo R, Gibbons W, Vlasses P, Ferguson R "Severe hypotension associated with concurrent clonidine and antipsychotic medication." Am J Psychiatry 142 (1985): 274. [PMID: 2857531]
3	Markowitz JS, Wells BG, Carson WH "Interactions between antipsychotic and antihypertensive drugs." Ann Pharmacother 29 (1995): 603-9. [PMID: 7663034]
4	Product Information. Abilify (aripiprazole). Bristol-Myers Squibb, Princeton, NJ.
5	Product Information. Clozaril (clozapine). Novartis Pharmaceuticals, East Hanover, NJ.
6	Product Information. Geodon (ziprasidone). Pfizer US Pharmaceuticals, New York, NY.
7	Product Information. Rexulti (brexpiprazole). Otsuka American Pharmaceuticals Inc, Rockville, MD.
8	Product Information. Risperdal (risperidone). Janssen Pharmaceutica, Titusville, NJ.
9	Product Information. Seroquel (quetiapine). Zeneca Pharmaceuticals, Wilmington, DE.
10	Product Information. Zyprexa (olanzapine). Lilly, Eli and Company, Indianapolis, IN.
11	White WB "Hypotension with postural syncope secondary to the combination of chlorpromazine and captopril." Arch Intern Med 146 (1986): 1833-4. [PMID: 3530167]