Details of Drug-Drug Interaction
| Drug General Information (ID: DDI2S3GRL6) | |||||||||
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| Drug Name | Droperidol | Drug Info | Lorcaserin | Drug Info | |||||
| Drug Type | Small molecule | Small molecule | |||||||
| Therapeutic Class | Antipsychotic Agents | Anorexiants | |||||||
| Structure | |||||||||
| Mechanism of Droperidol-Lorcaserin Interaction (Severity Level: Moderate) | |||||||||
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| CYP450 enzyme inhibition Click to Show/Hide Mechanism Graph | |||||||||
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| Drug Name | Droperidol | Lorcaserin | |||||||
| Mechanism 1 | CYP450 2D6 substrate | CYP450 2D6 inhibitor | |||||||
| Key Mechanism Factor 1 | |||||||||
| Factor Name | Cytochrome P450 2D6 |
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Structure
Sequence
MGLEALVPLAVIVAIFLLLVDLMHRRQRWAARYPPGPLPLPGLGNLLHVDFQNTPYCFDQLRRRFGDVFSLQLAWTPVVVLNGLAAVREALVTHGEDTADRPPVPITQILGFGPRSQGVFLARYGPAWREQRRFSVSTLRNLGLGKKSLEQWVTEEAACLCAAFANHSGRPFRPNGLLDKAVSNVIASLTCGRRFEYDDPRFLRLLDLAQEGLKEESGFLREVLNAVPVLLHIPALAGKVLRFQKAFLTQLDELLTEHRMTWDPAQPPRDLTEAFLAEMEKAKGNPESSFNDENLRIVVADLFSAGMVTTSTTLAWGLLLMILHPDVQRRVQQEIDDVIGQVRRPEMGDQAHMPYTTAVIHEVQRFGDIVPLGVTHMTSRDIEVQGFRIPKGTTLITNLSSVLKDEAVWEKPFRFHPEHFLDAQGHFVKPEAFLPFSAGRRACLGEPLARMELFLFFTSLLQHFSFSVPTGQPRPSHHGVFAFLVSPSPYELCAVPR
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| Gene Name | CYP2D6 | ||||||||
| Uniprot ID | CP2D6_HUMAN | ||||||||
| KEGG Pathway | hsa:1565 | ||||||||
| Protein Family | Cytochrome P450 family | ||||||||
| Protein Function |
A cytochrome P450 monooxygenase involved in the metabolism of fatty acids, steroids and retinoids (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:19965576, PubMed:20972997). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 20-hydroxyeicosatetraenoic acid ethanolamide (20-HETE-EA) and 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:18698000, PubMed:21289075). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Catalyzes the oxidative transformations of all-trans retinol to all-trans retinal, a precursor for the active form all-trans-retinoic acid (PubMed:10681376). Also involved in the oxidative metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
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| Mechanism Description |
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| Increased risk of hyperprolactinemia Click to Show/Hide Mechanism Graph | |||||||||
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| Drug Name | Droperidol | Lorcaserin | |||||||
| Mechanism 2 | Hyperprolactinemic effects | Hyperprolactinemic effects | |||||||
| Key Mechanism Factor 2 | |||||||||
| Factor Name | Hyperprolactinemia | ||||||||
| Factor Description | Hyperprolactinemia means that you have higher than normal levels of prolactin in your blood. Some people with hyperprolactinemia have very mild or no symptoms (asymptomatic), while others can suffer from infertility, loss of interest in sex, decreased bone mass, and silky discharge from the nipples in the absence of pregnancy or breastfeeding. | ||||||||
| Mechanism Description |
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| Recommended Action | |||||||||
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| Management | Caution is advised when lorcaserin is prescribed in combination with antipsychotics or other antidopaminergic agents (e.g., droperidol, domperidone, metoclopramide, phenothiazines, tetrabenazine). Clinicians, caregivers, and family members should be apprised of the risk of neuroleptic malignant syndrome and be alert to potential signs and symptoms such as mental status changes (e.g., mutism, catatonia, stupor, coma, agitation, confusion, hallucinations, delusions), autonomic instability, restlessness, rigidity, ataxia, myoclonus, hyperreflexia, tremors, diaphoresis, elevated creatine phosphokinase levels, and hyperpyrexia. If NMS is suspected, treatment with these agents should be discontinued immediately and emergency medical attention sought. Prolactin levels should be measured when there are signs and symptoms of prolactin excess such as galactorrhea or gynecomastia. Consideration should be given to discontinuation of prolactin-stimulating drugs including lorcaserin. | ||||||||
| References | |||||||||||||||||||
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| 1 | Product Information. Belviq (lorcaserin). Eisai Inc, Teaneck, NJ. | ||||||||||||||||||