Drugs and the perception of time

[Kdem]

There are a number of references, mostly the same text but rehashed.

I´m not sure how to add a PDF file , here is the thing: huguenardlab.stanford.edu/reprints/czp.pdf
gabaa, gabab, serotonin

Complicated and a lot. Perhaps see last paragraph on page 5. A reference to its effectiveness against absence seizures. I had great trouble understanding the first time I read it, I still do !

Here is something more simple: http://www.ncbi.nlm.nih.gov/pubmed/12736336

 

[Kdem]

About the CCK: I did not find any particular reference about clonazepam acting that way. I had read about cholecystokinin previously, and I did find articles like : http://www.ncbi.nlm.nih.gov/pubmed/8396038
Or http://www.ncbi.nlm.nih.gov/pubmed/7529711 , for whatever that´s worth.

At the dose of 2 mg clonazepam had a slight tendency to be anorexic. But that may be an individual thing.
I´m not sure why lorazepam tends to cause hunger, perhaps because of some action at the chemo receptor trigger zone ? I no longer have the references or data. It is given for nausea caused by chemotherapy.

 

[Epsilon Alpha]

About the CCK: I did not find any particular reference about clonazepam acting that way. I had read about cholecystokinin previously, and I did find articles like : http://www.ncbi.nlm.nih.gov/pubmed/8396038
Or http://www.ncbi.nlm.nih.gov/pubmed/7529711 , for whatever that´s worth.

At the dose of 2 mg clonazepam had a slight tendency to be anorexic. But that may be an individual thing.
I´m not sure why lorazepam tends to cause hunger, perhaps because of some action at the chemo receptor trigger zone ? I no longer have the references or data. It is given for nausea caused by chemotherapy.

I read through the PDF you posted, its an interesting study but as the effects on the thalamic reticular nuclei seem to be mediated via benzo sensitive GABA-A receptors it doesn't explain why these drugs could have differential effects on the the system. Now if I could find something giving the exact binding affinity to GABA-A receptors expressing various alpha subunits this could be a major player in the time perception as:

Within the thalamus, α1 and α3 are selectively expressed in the relay and reticular nuclei, respectively (Wisden et al., 1992; Pirker et al., 2000).

Unfortunately as my school cuts journal access following the regular semester I can't find full texts of of this, however I did find what looks like a decent source if you can find an open access copy. However, mentions that both drugs share roughly equivalent affinity for alpha1, alpha2, and alpha3 subunits as well as both are listed as a high affinity ligands for the gamma2 subunit. Unless this source is wildly incorrect or there is a confounding factor no one has noticed I think this kills the GABA-A subtype specific theory
https://wiki.tripsit.me/wiki/GABA_Receptors_and_Subunits_Info


So my thinking in the CCK vein is that structurally lorazepam resembles the stronger CCK receptor antagonist benzo's more closely than clonazepam. The release of at least peripheral CCK looks like its a class effect for anything binding to the omega BZD site. With that said however, if lorazepam originally produced less CCK receptor activation due to antagonism of the receptor we could expect an increase in appetite especially in a clonazepam tolerant individual assuming my assumption on the structural activity relations is correct.

There is also conflicting data regarding benzodiazepines in 50ug CCK-4 induced anxiety/panic challenge, with 1mg alprazolam proving effective but 1mg lorazepam proving ineffective (though alprazolam is roughly twice as potent as lorazepam and having a markedly different structure).

 

[Kdem]

That wiki discusses affinity in words (moderate, high). I wonder if there is a source that has actual numbers ?

Because lorazepam had hypnotic, sedative and amnestic properties that clonazepam had not, not even close !

Here is another one: http://www.ncbi.nlm.nih.gov/pubmed/7931539
It specifically refers to clonazepam's action on GABAB.

My knowledge about neurology is very limited, but I know that baclofen inhibits serotonin release.
Serotonin could modulate neurotransmitters like norepinephrine. High levels of norepinephrine may seem time to pass slower.

Perhaps a specific combination of affinity to the GABAA receptors does play a role ?
Not only alpha2 affinity, but also gamma2 affinity, in some specific combination (numbers) ?
But I'm guessing.
There are some distinct differences between the two drugs, and it's not just duration of action.