Inappropriate uncontrollable laughing or crying is common in many neuroscience medicine disorders including after traumatic brain injury or stroke. It can be socially embarrassing and restrict opportunities for social interaction.
This loss of control over emotional responses is known by the term pseudobulbar affect or PBA. Until recently, few therapeutic options were available to treat this condition.
Now a relatively new drug Nuedexta uses a combination of dextromethorphan and quinide to treat pseudobulbar affect. This drug combination has received FDA approval in the U.S.
A recent review article summarized what is known about the pharmacology of the drug dextromethorphan (DM). DM is found in over-the-counter cough medications, for example Robitussin DM.
The DM mechanism of action is felt to be due to the blocking of the NMDA receptor (N-methyl-D-aspartate). This results in a inhibition of the excitotoxic neurotransmitter glutamate. The effect of DM on neurotransmitter function is non-specific and effects on other neurotransmitter systems include:
- Inhibition of serotonin reuptake
- Inhibition of norepinephrine uptake
- Antagonism of the nicotinic acetylcholine receptors
- Agonism of sigma1-R gene
Quinidine inhibits CYP2D6 the cytochrome P450 liver enzyme involved in liver enzyme metabolism of DM. This results in much higher and prolonged blood levels of dextromethorphan.
The potential therapeutic targets for DM mentioned in the review include the following:
- Pseudobulbar affect
- Epilepsy
- Pain
- Peripheral neuropathy
- TBI
- Stroke
- Alzheimer’s disease (agitation)
I will take a look at some of the specific research studies in these additional targets over the next week or two.
Follow the author on Twitter WRY999
Figure of Advertising Card showing phases of laughter is from Wikipedia Creative Commons.
By not known, printed by Young's, The Hatter - eBay store Web page: http://ebay.to/29rwilh
Taylor CP, Traynelis SF, Siffert J, Pope LE, & Matsumoto RR (2016). Pharmacology of dextromethorphan: Relevance to dextromethorphan/quinidine (Nuedexta®) clinical use. Pharmacology & therapeutics PMID: 27139517
No comments:
Post a Comment