The best explanation I could find is that levetiracetam attaches to SV2A on the surface of the neuron vesicles, and that this attachment reduces the backlog of signals that cause a seizure. How exactly does it reduce the overload of signals?
Hi Abby,
The mechanisms of action of Keppra is not fully understood. However, besides SV2A-mediated effects, levetiracetam may also affect presynaptic calcium channels and reduce glutamate release. For a recent Mini-Review and references therein, see http://journal.frontiersin.org/Journal/10.3389/fncel.2014.00164/full .
Best,
Jochen
LEV binds to the SV2A protein in the vesicle walls that contain glutamate. Thereby the fusion of these vesicles with the cell membrane is impaired and, thus, the exocytosis of glutamate is reduced.
Hi Arne,
Interesting! Do you know a reference paper for that?
Best,
Jochen
Please see the attached paper. Jump right to the discussion, first paragraph.
I should of course add that nothing is 100% proven, but available evidence makes this model the most likely explanation. ;)
Agree, but evidence in the PNAS paper is indirect and does not rule out voltage-gated channels associated with SV2a as LEV targets. SV2a is expressed at both Glu and GABA synapses, which makes a purely SV2a-dependent LEV mechanism difficult to explain - e.g. see: PubMed-ID 22046416 or 22847229 ? Anyway, the most important finding probably is that it acts at the presynaptic level of synaptic communication :-) ... Cheers, Jochen
I agree with you, Jochen. Of course this paper does not rule out other mechanisms, and ion channels are very likely to be affected. In fact, I do think that virtually all drugs are "dirty drugs". They all have multiple mechanisms of action. One may be more important than others, but I do not buy the concept of "one mechanism of action only". History shows that if you only search long enough, you'll find.
Anyway, as you said, the most exciting thing here is the novel presynaptic MOA.
totally agree, epilepsy is a multifactorial disease and Keppra action certainly involves different mechanisms...
I wonder what will happen when someone without epilepsy and besides a low glutamate level takes levetiracetam.
Does this have any positive effects or will it be unhealthy?
Mark, this might be of interest to you: http://www.ncbi.nlm.nih.gov/pubmed/21683631
Hi Ward,
Thank you for sharing! It's interesting that you suggest treatment with Levetiracetam and mention its potential as a cognitive enhancer. I knew a patient who was given Levetiracetam for seizures and who had a significant and rapid decline in short term memory, concentration, motor movements, and a sudden onset of behavioral problems for several months following the prescription. It was assumed these changes were side effects of the Levetiracetam, since they began shortly after it was prescribed and had not been noted before beginning the treatment.
The cause of the seizures in the patient was never diagnosed, and it was unclear which symptoms were side effects of treatment and which were effects of the illness itself. This makes me wonder if the symptoms described were actually not caused by the Levetiracetam, as assumed at the time, but by the disease itself (which could provide more clues leading to an eventual diagnosis).
Thanks for sharing,
-Abigail
Hi, Abigail Danfora Ward Dean ,
My father suffering from such these complications since two years ago and was given Levetiracetam 3000 mg/day for seizures with another types of AEDs for instance; Phenobarbital 150 mg/day. he is a bedridden since that.
in April 2018 he infected he had aspiration pneumonia which was followed to the intensive care unit and was dealt with through the doctor of the respiratory system in addition to a neurologist
He took two types of antibiotics
Ciprofloxacin and gentamycin
Because of any interaction between keppra and gentamycin , the doctors decided to reduce the keppra dose by half
That period - before the occurrence of inflammation of the chest - (2000 mg) divided into two morning and evening
After the dose reduction my dad took 1000 mg divided into two morning and evening periods as well
The following was observed within three days of the beginning of the reduction
1. It is the most noticeable and is the speed of movement and response
2. He sits balanced on the edge of the bed
3. Recovery and psychological improvement
Q: Is this activity related to reduction of the dose of keppra, noting that the remaining drugs have not been reduced any of them?