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Monoamine oxidase inhibitory properties of milacemide in rats
D D Truong1, B Diamond, G Pezzoli
1Department of Neurology, Columbia University College of Physicians and Surgeons, New York, N.Y. 10032.
Abstract:
Milacemide is a glycine prodrug with reported antiepileptic antimyoclonic properties. In this study, milacemide increased "wet dog shakes" in rats pretreated with 5-Hydroxytryptophan (5-HTP) and carbidopa. Moreover, it worsened the serotonin behavior syndrome precipitated by 5-HTP and the monoamine oxidase inhibitor tranylcypromine. The serotonin syndrome was also elicited by the combination of milacemide and 5-HTP without tranylcypromine. In vitro, milacemide inhibited both monoamine oxidase A and B from the frontal cortex of rats, to a greater extent for MAO B. This drug is currently under investigation in humans as an antiepileptic agent and precautions for the consequences of monoamine oxidase inhibition should be considered when the drug is used in high doses.
Insights
Milacemide, an antiepileptic drug, exacerbated serotonin syndrome in rats. This glycine prodrug also inhibited monoamine oxidase A and B, suggesting caution at high doses.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Milacemide is a glycine prodrug investigated for antiepileptic and antimyoclonic effects.
- Serotonin syndrome is a potentially life-threatening condition associated with excessive serotonergic activity.
Purpose of the Study:
- To investigate the effects of milacemide on serotonin-related behaviors in rats.
- To determine the in vitro inhibitory effects of milacemide on monoamine oxidase (MAO) enzymes.
Main Methods:
- Administered milacemide to rats pretreated with 5-Hydroxytryptophan (5-HTP) and carbidopa.
- Induced serotonin syndrome using 5-HTP with tranylcypromine or milacemide.
- Assessed MAO-A and MAO-B inhibition by milacemide in rat frontal cortex homogenates in vitro.
Main Results:
- Milacemide increased "wet dog shakes" in rats treated with 5-HTP and carbidopa.
- Milacemide worsened serotonin behavior syndrome induced by 5-HTP and tranylcypromine.
- Milacemide also elicited serotonin syndrome when combined with 5-HTP alone.
- In vitro, milacemide demonstrated inhibition of both MAO-A and MAO-B, with greater potency against MAO-B.
Conclusions:
- Milacemide possesses properties that can precipitate or worsen serotonin syndrome.
- The drug inhibits both MAO-A and MAO-B, suggesting a potential mechanism for its observed effects.
- Clinical use of milacemide, especially at high doses, warrants consideration of potential monoamine oxidase inhibition consequences.