Lorazepam with Magnolia Interaction Details
Brand Names Associated with Lorazepam
- Ativan®
- Lorazepam
- Lorazepam Intensol®
- Loreev XR®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 13, 2023
Interaction Effect
Increased central nervous system depression
Interaction Summary
Magnolia bark constituents magnolol and honokiol exert central nervous system depression in animals. Effects are likely to be of short duration with a half-life of 49 to 56 minutes observed in rats . The effects of honokiol, an active constituent of magnolia, were reversed following administration of flumazenil . Therefore, the central nervous system activity of magnolia may be similar to that of benzodiazepines. Caution is advised if magnolia bark and a benzodiazepine are taken concomitantly, as the patient may experience excessive central nervous system depression.
Severity
Minor
Onset
Delayed
Evidence
Theoretical
How To Manage Interaction
If patients elect to take these compounds concomitantly, they should avoid operating heavy machinery or driving until the magnitude of the effect is known.
Mechanism Of Interaction
Possibly stimulation of GABA-A receptors
Literature Reports
A) Honokiol, a neolignane derivative present in magnolia bark, has central nervous system depressant activity and at lower doses, anxiolytic activity. Anxiolytic activity (as shown by prolonged time spent in the open arms of the maze) was noted in a plus-maze test in mice of a single oral dose of 20 milligrams/kilogram (mg/kg) honokiol (p less than 0.05). Honokiol did not affect traction performance, whereas diazepam 0.5 mg/kg to 2 mg/kg prolonged time spent in open arms of the maze and disrupted traction performance. After 7 days of treatment with 0.2 mg/kg honokiol and after a single treatment with 1 mg/kg diazepam, performance in the plus-maze was nearly equivalent. The effect of honokiol was reversed following subcutaneous administration of flumazenil 0.3 mg/kg. Combination treatment with honokiol and diazepam significantly prolongd the time spent in open arms of the maze over treatment with either alone (p less than 0.05). Honokiol reduced the effect of diazepam on motor activity, but did not affect diazepam-induced inhibition of traction performance. The authors concluded based on their findings that honokiol induces an anxiolytic effect with less liability of causing sedation, disinhibition, or motor dysfunction than diazepam. Possible mechanisms proposed were that honokiol selectively stimulates GABA-A receptors, or honokiol binds to other sites related to the anxiolytic effect .
B) Honokiol administered intravenously to 5 rats resulted in an elimination rate constant of 0.08 +/- 0.01 Liters/minute (L/minute) after a 5 mg/kg loading dose, and 0.06 +/- 0.02 L/minute after a 10 mg/kg loading dose. Half-life was 49.22 +/- 6.78 minutes after a 5 mg/kg loading dose, and 56.24 +/- 7.30 minutes after a 10 mg/kg loading dose. The bioavailability as expressed as area under the curve (AUC) was 58.87 +/- 4.19 micrograms/milliliter/minute (mcg/mL/minute) after a 5 mg/kg loading dose, and 133.89 +/- 16.26 mcg/mL/minute (p less than 0.05) after a 10 mg/kg loading dose .
C) Magnolol and honokiol at 100 mg/kg, 200 mg/kg, and 400 mg/kg administered intraperitoneally to mice suppressed grip strength in a dose-dependent manner. Grip strength was lost within 30 minutes, which was sustained for 3 hours after a 400 mg/kg dose of either compound. Spinal reflexes in the chick were inhibited in a dose-dependent manner with magnolol and honokiol at 12.5 mg/kg, 25 mg/kg, 50 mg/kg, and 100 mg/kg intraperitoneally .
D) Magnolol and honokiol may cause depression of the ascending activating systems and the spinal cord based on mice studies demonstrating sedation, ataxia, muscle relaxation, and anticonvulsant activities of magnolol and honokiol. Magnolol at 63 mg/kg intraperitoneally produced hypomotility, ptosis, and sedation. Magnolol 125 mg/kg produced sedation, ataxia, and muscle relaxation; at 250 mg/kg magnolol produced ataxia, loss of righting reflex, and muscle relaxation of 4 legs. Honokiol produced similar effects at 125 mg/kg, 250 mg/kg, and 500 mg/kg. Both magnolol and honokiol compounds at 50 mg/kg suppressed spinal reflexes in chicks. In mice, pretreatment with magnolol 100 mg/kg inhibited tonic extensor convulsion and death induced by an intracerebroventricular injection of penicillin G potassium 50 micrograms (mcg) .
E) The ether extract of magnolia bark and its purified constituents, magnolol and honokiol were examined in terms of muscle relaxant properties in the mouse model. Magnolol at 100 mg/kg produced muscle relaxation for 2 hours; magnolol 250 mg/kg induced loss of righting reflex and muscle relaxation extending beyond 3 hours. Honokiol 250 mg/kg exhibited muscle relaxation properties for 3 hours with 500 mg/kg producing loss of righting reflex. Muscle relaxing properties of both compounds subsided fully within 24 hours after injection. The ether extract at 1 gram/kg induced loss of righting reflex 30 minutes after injection for nearly 60 minutes .
Lorazepam Overview
-
Lorazepam is used to relieve anxiety. Lorazepam is also used to treat insomnia caused by anxiety or temporary situational stress. Lorazepam is in a class of medications called benzodiazepines. It works by slowing activity in the brain to allow for relaxation.
Return To Our Drug Interaction Homepage
Feedback, Question Or Comment About This Information?
Ask Dr. Brian Staiger, PharmD, our medical editor, directly! He's always more than happy to assist.
Definitions
Severity Categories
Contraindicated
These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.
Major
This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.
Moderate
This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.
Minor
While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.
Onset
Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.
Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.
Evidence
Level of documentation of the interaction.
Established: The interaction is documented and substantiated in peer-reviewed medical literature.
Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.
How To Manage The Interaction
Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.
It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.
Mechanism Of Interaction
The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.
Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.
Where Does Our Information Come From?
Information for our drug interactions is compiled from several drug compendia, including:
The prescribing information for each drug, as published on DailyMED, is also used.
Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.
The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.