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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 10 of 10. This is the beginning of the thread.
Posted by jrbecker on September 20, 2005, at 9:01:03
who funds this stuff? talk about confirming the obvious....
Caffeine Partially Counteracts Sedation Effects of Zolpidem (Ambien)
By Crystal PhendWASHINGTON, DC -- September 19, 2005 -- Taking the sleep aide zolpidem (Ambien) with a can of soda or coffee could reduce the drug's effectiveness, according to researchers who presented study results at the American College of Clinical Pharmacology (ACCP) here on September 11th.
A high dose of caffeine -- 500 mg or the equivalent of four cups of coffee -- reduced the effect of zolpidem by two thirds, according to subjective measures, said lead author Dora Farkas, PhD, a post-doctoral fellow, Department of Pharmacology and Experimental Therapeutics, Tufts University, Boston, Massachusetts, United States.
Although the effects of caffeine on the sedative effects of benzodiazepine agonists such as zolpidem have been theorized, the interaction was never confirmed by a controlled study.
In the double-blind study, Dr. Farkas and colleagues evaluated 12 healthy subjects who received 500 mg or 250 mg of caffeine or placebo, as well as a 7.5 mg dose of zolpidem, in a 6-way crossover design such that each person received each combination.
Observers and participants reported the level of sleepiness after taking each combination in addition to ranking other subjective measures like anxiety level. Plasma levels of the two drugs were measured. An electroencephalogram (EEG), digit substitution test and 16-item word-list memory test were also used to rate sedation.
Low and high dose caffeine partially reversed the sedation effects of zolpidem. High dose caffeine caused a 3- to 4-fold reduction in fatigue. The clearance of caffeine from plasma was reduced by zolpidem but not significantly so.
There was no significant difference in beta-EEGs with coadministration of caffeine and zolpidem. Subjective ratings indicated that patients felt more anxious as the caffeine dose increased with zolpidem.
Dr. Farkas said the pharmacokinetic interaction was smaller than expected but the pharmacodynamic effects of co-administration were greater than anticipated.
[Presentation title: Pharmacokinetic and Pharmacodynamic Interactions Between Zolpidem and Caffeine. Abstract 61]
Posted by Bill LL on September 20, 2005, at 10:49:25
In reply to Caffeine Partially Counteracts Sedationfrom Ambien, posted by jrbecker on September 20, 2005, at 9:01:03
I drank tea with caffeine last night, then took 2 mg of Lunesta. The Lunesta did not work as well as usual. I guess it's just common sense not to drink caffeine near bed time if one has a sleeping issue. But that shows how much common sense I have! From now on, no caffeine for me after 6 pm.
Posted by SLS on September 20, 2005, at 12:50:45
In reply to Caffeine Partially Counteracts Sedationfrom Ambien, posted by jrbecker on September 20, 2005, at 9:01:03
> who funds this stuff? talk about confirming the obvious....
>
>
> Caffeine Partially Counteracts Sedation Effects of Zolpidem (Ambien)
> By Crystal Phend
It would be interesting to know if taking Provigil (modafinil) would be equally antagonistic to the hypnotic effects of zolpidem.Speaking of orexin, I recently read something that suggested orexinergic activity might be partially responsible for the experience of reward and reward-seeking behavior. I wish I could remember where I saw it. Perhaps it is through orexin that modafinil produces its antidepressant effects, and not through glutamate. Maybe manipulating orexin would help in the treatment of substance abuse.
- Scott
Posted by jrbecker on September 20, 2005, at 13:39:10
In reply to Re: Caffeine Partially Counteracts Sedationfrom Ambien, posted by SLS on September 20, 2005, at 12:50:45
> > who funds this stuff? talk about confirming the obvious....
> >
> >
> > Caffeine Partially Counteracts Sedation Effects of Zolpidem (Ambien)
> > By Crystal Phend
>
>
> It would be interesting to know if taking Provigil (modafinil) would be equally antagonistic to the hypnotic effects of zolpidem.
>
> Speaking of orexin, I recently read something that suggested orexinergic activity might be partially responsible for the experience of reward and reward-seeking behavior. I wish I could remember where I saw it. Perhaps it is through orexin that modafinil produces its antidepressant effects, and not through glutamate. Maybe manipulating orexin would help in the treatment of substance abuse.
>
>
> - Scott
You're probably referring to this...
http://www.sciencedaily.com/releases/2005/08/050827140339.htmSanofi's got a few orexin antagonists in preclinical trials. Of course, realize these are drugs that will inhibit the effect orexin has on pleasure. Might be good for drug withdrawal but not treatment-resistant depression.
Posted by SLS on September 20, 2005, at 23:12:03
In reply to Re: Caffeine Partially Counteracts Sedationfrom Ambien » SLS, posted by jrbecker on September 20, 2005, at 13:39:10
Hi JB.
> > Speaking of orexin, I recently read something that suggested orexinergic activity might be partially responsible for the experience of reward and reward-seeking behavior. I wish I could remember where I saw it. Perhaps it is through orexin that modafinil produces its antidepressant effects, and not through glutamate. Maybe manipulating orexin would help in the treatment of substance abuse.
> You're probably referring to this...
> http://www.sciencedaily.com/releases/2005/08/050827140339.htmNo, I hadn't seen this article. I was just guessing at the substance abuse stuff.
> Sanofi's got a few orexin antagonists in preclinical trials. Of course, realize these are drugs that will inhibit the effect orexin has on pleasure. Might be good for drug withdrawal but not treatment-resistant depression.
From the article:
"Using rPP, a neuropeptide that activates orexin neurons in the lateral hypothalamus, the researchers were able to reinstate drug seeking in the rats formerly possessing extinguished drug-seeking behavior."
Might this peptide prevent or reverse learned helplessness, thus indicating antidepressant properties?
Would you happen to know if there is any connection between orexin/hypocretin and HPA axis activity? Perhaps chronic low orexin leads to increased HPA activity and increased cortisol production? I'm really reaching on this one.
- Scott
Posted by zeugma on September 21, 2005, at 5:12:59
In reply to Re: Caffeine Partially Counteracts Sedationfrom Ambien » jrbecker, posted by SLS on September 20, 2005, at 23:12:03
Would you happen to know if there is any connection between orexin/hypocretin and HPA axis activity? Perhaps chronic low orexin leads to increased HPA activity and increased cortisol production? I'm really reaching on this one.>>
Orexin is crucially involved in HPA function:
It seems from reading these abstracts that the HPA axis is activated by orexin, but possibly a orexin deficiency in orexin could cause a compensatory rise in HPA activity from some other source.
Modafinil is being used as a treatment for substance abuse:
Modafinil's activation of orexin receptors appears to be secondary to its ability to release histamine (the orexinergic system is activated by histamine). I would bet that modafinil's actions on histamine are responsible for a lot of its side effects, as well as its therapeutic action. Modafinil strongly activates the tuberomammillary nucleus, which is the site of all histamine projections in the brain.
My pdoc claims that modafinil's primary action is on histamine.
-z
Posted by zeugma on September 21, 2005, at 16:09:05
In reply to modafinil » SLS, posted by zeugma on September 21, 2005, at 5:12:59
I would believe that modafinil is pro-histaminic, from the intensity of hay fever symptoms I'm experiencing.
I went through an entire box of Kleenex today at work. Modafinil is an unpleasant drug.
-z
Posted by SLS on September 21, 2005, at 17:54:24
In reply to modafinil » SLS, posted by zeugma on September 21, 2005, at 5:12:59
Hi Z.
Thanks for all the information.
> Modafinil's activation of orexin receptors appears to be secondary to its ability to release histamine (the orexinergic system is activated by histamine).
I thought it was the other way around. Oh well.
BTW, Charles Dackis was my doctor on two separate occasions. I didn't realize that he had focused so much on drug abuse.
- Scott
Posted by zeugma on September 21, 2005, at 19:51:48
In reply to Re: modafinil » zeugma, posted by SLS on September 21, 2005, at 17:54:24
> Modafinil's activation of orexin receptors appears to be secondary to its ability to release histamine (the orexinergic system is activated by histamine).>>
I thought it was the other way around. Oh well.>
It seems that we're both right, and interactions are reciprocal between the two systems:
Orexin/hypocretin excites the histaminergic
neurons of the tuberomammillary nucleus
by
Eriksson KS, Sergeeva O, Brown RE, Haas HL.
Institute for Neurophysiology,
Heinrich-Heine-Universitat,
D-40225 Dusseldorf, Germany.
J Neurosci 2001 Dec 1;21(23):9273-9ABSTRACT
The hypothalamic orexin (hypocretin) neuropeptides are associated with the regulation of sleep and feeding, and disturbances in orexinergic neurotransmission lead to a narcoleptic phenotype. Histamine has also been shown to play a role in the regulation of sleep and feeding. Therefore, we studied the relationship between the orexin and histamine systems of the CNS using electrophysiology, immunocytochemistry, and the reverse transcriptase (RT)-PCR method. Both orexin-A and orexin-B depolarized the histaminergic tuberomammillary neurons and increased their firing rate via an action on postsynaptic receptors. The depolarization was associated with a small decrease in input resistance and was likely caused by activation of both the electrogenic Na(+)/Ca(2+) exchanger and a Ca(2+) current. In a single-cell RT-PCR study using primers for the two orexin receptors, we found that most tuberomammillary neurons express both receptors and that the expression of the orexin-2 receptor is stronger than that of the orexin-1 receptor. Immunocytochemical studies show that the histamine and orexin neurons are often located very close to each other. The contacts between these two types of neurons seem to be reciprocal, because the orexin neurons are heavily innervated by histaminergic axons. These results suggest a functional connection between the two populations of hypothalamic neurons and that they may cooperate in the regulation of rapid-eye-movement sleep and feeding.-z
Posted by Chairman_MAO on September 22, 2005, at 10:21:30
In reply to Caffeine Partially Counteracts Sedationfrom Ambien, posted by jrbecker on September 20, 2005, at 9:01:03
Add a high dose of l-theanine (adenosine agonist) and this will be ameliorated.
This is the end of the thread.
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