Melatonin and Keppra

Hi,

I am curious what experience people have combining melatonin and keppra (500 mg). I'd be taking 4-5 mg of melatonin and moving up maybe in the range of 16 mg. I find my timing with Keppra to be around 9am/9pm and my melatonin timing to be considerably later at around 12:30 am. 

On my supplement package it says that I should speak to my doctor if I am taking epilepsy drugs (keppra). The one study that I can find on pubmed indicates that they antagonize each other. I added the study below. I gave a list of supplements to my doctor last week, hopefully he gets around to it soon.

Do you guys have any thoughts on melatonin and keppra? What is the maximum dose that you can tolerate per kg?

Cool,

Fahd.

Naftalin RJ, Cunningham P, Afzal-Ahmed I.

Physiology Division, Centre for Vascular Biology and Medicine, King's College London, Guy's Campus, New Hunt's House, London SE1 1UL. Richard.Naftalin@kcl.ac.uk

1 Nootropic drugs increase glucose uptake into anaesthetised brain and into Alzheimer's diseased brain. Thyrotropin-releasing hormone, TRH, which has a chemical structure similar to nootropics increases cerebellar uptake of glucose in murine rolling ataxia. This paper shows that nootropic drugs like piracetam (2-oxo 1 pyrrolidine acetamide) and levetiracetam and neuropeptides like TRH antagonise the inhibition of glucose transport by barbiturates, diazepam, melatonin and endogenous neuropeptide galanin in human erythrocytes in vitro. 2 The potencies of nootropic drugs in opposing scopolamine-induced memory loss correlate with their potencies in antagonising pentobarbital inhibition of erythrocyte glucose transport in vitro (P<0.01). Less potent nootropics, D-levetiracetam and D-pyroglutamate, have higher antagonist Ki's against pentobarbital inhibition of glucose transport than more potent L-stereoisomers (P<0.001). 3 Piracetam and TRH have no direct effects on net glucose transport, but competitively antagonise hypnotic drug inhibition of glucose transport. Other nootropics, like aniracetam and levetiracetam, while antagonising pentobarbital action, also inhibit glucose transport. Analeptics like bemigride and methamphetamine are more potent inhibitors of glucose transport than antagonists of hypnotic action on glucose transport. 4 There are similarities between amino-acid sequences in human glucose transport protein isoform 1 (GLUT1) and the benzodiazepine-binding domains of GABAA (gamma amino butyric acid) receptor subunits. Mapped on a 3D template of GLUT1, these homologies suggest that the site of diazepam and piracetam interaction is a pocket outside the central hydrophilic pore region. 5 Nootropic pyrrolidone antagonism of hypnotic drug inhibition of glucose transport in vitro may be an analogue of TRH antagonism of galanin-induced narcosis.

Fahd,

Very interesting.  Let us know what your NO says.  Does this mean that keppra or the generic allow glucose where melatonin counters it?  The article a little to techie for me.  I do know that glucose helps tumors get energy to grow so how does this fit in? 

Thanks for any info., Donna, wife of Rob dx 12/08, recurrance 7/09

my young daughter just started taking Melatonin for inability to sleep through the night. She is coming up on being a 7yr survivor. Inability to sleep has been going on for years. Was using Clonodine but it didnt work.

as far as being Epilepsy drugs........the seizures she has are classified as epilieptic- genetic type. But there is no history in the family of epilepsy. I think basically any number of seizures is classified as Epileptic in nature.Thus the use of "Epileptic" meds. 

On 10/14/2009 madonnav wrote:

Fahd,

Very interesting.  Let us know what your NO says.  Does this mean that keppra or the generic allow glucose where melatonin counters it?  The article a little to techie for me.  I do know that glucose helps tumors get energy to grow so how does this fit in? 

Thanks for any info., Donna, wife of Rob dx 12/08, recurrance 7/09

Hmm, I had not thought of it from that perspective: glucose transport bridge. I will call him tomorrow. It jives with what I know of the racetams--that they increase cognitive ability. In fact, I was taking piractem and aniractam for some months before my first seizure. I asked my doctor if my taking those 2 drugs limited my seizures and (thus my finding out about my tumor) and he indicated that they worked on different principles. However much of the consequent information I've found on the internet indicates as much.

For example: 

 Effects of Piracetam alone and in combination with antiepileptic drugs in rodent seizure models

 Fischer, W etc.

Rudolf-Boehm-Institute of Pharmacology and Toxicology, University of Leipzig, Germany. fisw@medizin.uni-leipzig.de

The
nootropic drug piracetam was investigated in various experimental
models of epilepsy. Generally, piracetam exhibits no or only moderate
anticonvulsant properties against generalized tonic or clonic seizures.
However, in many cases it did increase the anticonvulsant effectiveness
of conventional antiepileptics, as shown in the maximal electroshock
seizure (MES) threshold test, the traditional MES test or in DBA/2
mice. A pharmacokinetic interaction does not seem to be responsible for
this effect. In lethargic mice, a model of absence seizures, piracetam
significantly decreased the incidence and duration of spike-wave
discharges. Furthermore, in the cobalt-induced focal epilepsy model
piracetam reduced the number of spikes/min and in the hippocampal
stimulation model it increased the anticonvulsant potency of
phenobarbital and phenytoin after single and repeated administration.
In conclusion, the well tolerated piracetam itself did not show marked
anticonvulsant effects in most screening tests, however, its
co-medication with antiepileptic drugs improved seizure protection in
various models which may bear potential clinical significance.

PMID: 15338329

Obviously a rodent study, especially with neurology doesn't indicate much for humans but this study was done with humans:

Montreal Neurological Institute and Hospital, 

3801 University St, Room 127,

Montreal, Quebec, Canada H3A 2B4.

Arch Neurol 2001 May;58(5):781-6



Abstract

BACKGROUND: Piracetam has been proven to be effective and well tolerated in the treatment of myoclonus in short-term studies. 

OBJECTIVE: To assess its long-term
clinical efficacy, 11 patients with disabling myoclonus due to
progressive myoclonus epilepsy were treated with
piracetam in an open-label study.

METHODS: Neurologic outcome (at the 1st,
6th, 12th, and 18th month of treatment) was assessed by an adjusted sum
score of the following 3 indices: motor impairment, functional
disability, and global assessment of disability due to myoclonus.
Severity of other neurologic symptoms (seizure frequency and severity,
dysarthria, and gait ataxia) also was assessed. Treatment with
piracetam was initiated at a dose of 3.2
g/d that was gradually increased until stable benefit was noted
(maximal dose in the trial was 20 g/d). Concomitant antiepileptic drugs
were maintained at their previous dose.

RESULTS: Statistically significant improvement in the total rating score was
observed after introduction of piracetam
at the 1st, 6th, and 12th month of treatment. Severity of other
neurologic symptom scores did not improve significantly. Two patients
reported drowsiness during the first 2 weeks of treatment.

CONCLUSIONS: Piracetam given
as add-on therapy seems to be an effective, sustained, and
well-tolerated treatment of myoclonus. In patients with progressive
myoclonus epilepsy, the efficacy of the drug increased during the first
12 months of treatment and then stabilized.

Etc. 

So, anyone taking melatonin and levetiracetam?? Effects. 

Hi,

I spoke to my NO (or actually his fellow) and he told me it was ok. He looked at the full paper and the point where they antagonize each other doesn't have anything to do with its anti-seizure properties. A bit of a relief. 

 Will continue to report.