• Neuroscience & Pharmacology Discussion Welcome Guest
    Posting Rules Bluelight Rules
    Recent Journal Articles Chemistry Mega-Thread
    FREE Chemistry Databases! Self-Education Guide

  • N&PD Moderators: Skorpio | someguyontheinternet

Classics in Chemical Neuroscience: Amitriptyline

bigjackaal96 said:
Depression Is basically ACH hyperactivity which would explain why TCA's are very potent. Amitriptyline also a potent SNRI which would repair the damage to bowels. I wonder how many cases of Autism from doctors throwing out SRI's like candy since they still affect 5HT2 in the same way as Psychs do.
Click to expand...
how does an SNRI aid in repair of the bowel, what is the mechanism?

are you suggesting that autism is caused by serotonin reuptake inhibitors as well as serotonergic psychedelics?
 
someguyontheinternet said:
how does an SNRI aid in repair of the bowel, what is the mechanism?

are you suggesting that autism is caused by serotonin reuptake inhibitors as well as serotonergic psychedelics?
Click to expand...
It forces the body to keep the excess serotonin as a back up pathway when non-CNS ACH Is very low. Noticed this when I had FAR less IBS episodes with DPH at 25 ~ 125mg. I know It not mild food poisioning or true IBS, Because It happens even on days when I've not ate anything till dinner.
 
Last edited:
bigjackaal96 said:
It forces the body to keep the excess serotonin as a back up pathway when non-CNS ACH Is very low. Noticed this when I had FAR less IBS episodes with DPH at 25 ~ 125mg. I know It not mild food poisioning or true IBS, Because It happens even on days when I've not ate anything till dinner.
Click to expand...

Wait. You are presenting your own opinions on your own subjective symptoms as evidence backed by no tests whatsoever as evideince?

It has a term and it's not evidence - it's called hearday.
 
4DQSAR said:
Well, I can only speak of the UK. I'm uncertain what the legal position of the stuff IS in the US. Is it prescription only or is it simply so old that nobody sells it any more. I mention that because a couple of quite legal antihistamines such as cyclizine are still in theory available from a pharmacy, none of them stock it. It's not a prescriptiom medicine, it's just died out because nobody was buying.
Click to expand...

It’s prescription only. But rarely used outpatient exception for treatment of hyperemesis gravidarum. If you ask for it specifically, you get the stink eye as it is regarded as suspiciously popular with junkies. Basically you have to be pregnant or allergic to Zofran to get a prescription.
 
4DQSAR said:
I can believe it. No doubt someone had noted that amtohistamines such as promethazine had quite a robust antidepressant action BUT was not optimized for that indication.

I wonder if the competition was for the FIRST synthesis so that one partly holds the patent rights OR was it the fact that their success meant a 'lively' industry in finding cheaper synthetic routes culminated with echical standards even lower than is common to medicinal chemists?
Click to expand...
This is the citation that was provided:
Protiva M. Recent progress in the pharmaco-chemical research on antihistamine drugs and psychotropic agents- derivatives of tricyclic systems having a seven or eight-membered middle ring. Farmaco Sci. 1966 Jan;21(1):76-104. PMID: 5328535.
Click to expand...
File wrapper of US patent application, S.N. 802,298, filed March 27, 1959, now US patent 3,384,663, issued to G. Rey-Bellet and H. Spiegelberg and assigned to Hoffmann-LaRoche. Other applications cited in the file wrapper are: (a) S.N. 855,981, E.L. Engelhard (Merck), filed Nov 30, 1959, now US3428735 (b) S.N. 828,722, F. J. Villani (Schering), filed July 22, 1959; think it's this one US3409640 (c) S.N. 27,267, S. O. Winthrop (Ayerst), filed May 6, 1960; could find this CA717977A (d) J. Mills (Lilly), filing date and serial number not disclosed. corresp. to US3189657
Click to expand...
 
Last edited:
Well, that's clearly before the class were approved for human use so it would seem that mamy researchers were all trying to patent the same 'novel' compounds.

I wonder if there was an academic paper that noted that something like promethazine had been tested and shown to posess robust antidepressant activity and everyone hurrifly carried out the same research in parallel?

Or industrial espionage took place. A friend worked at a US pharmacutical conglomerate for a while. Their job was instrumental analysis (so pity them) and the lab they worked in paid private investigators to poke through the refuse from the other labs owned by said conglomerate with a view to stealing ideas.

Apparently they were all told 'Other pharmacitical manufacturers are the competition - the other labs within OUR conglometate are the enemy'. And they meant it.

I hve only mentioned a tiny fraction of the things I've seen and the things friends have told me, but there is so much money at stake, there is almost nothing they won't do to get that patent. I've never heard of anyone getting threatened or worse... but it wouldn't surprise me. If they are prepared to use private investigators, they WILL have boxed every single person in each team. So if a threat was made, would we ever hear of it?
 
SeekingOblivion said:
It’s prescription only. But rarely used outpatient exception for treatment of hyperemesis gravidarum. If you ask for it specifically, you get the stink eye as it is regarded as suspiciously popular with junkies. Basically you have to be pregnant or allergic to Zofran to get a prescription.
Click to expand...
To clarify for non-US, codeine (w/ promethazine) cough syrup's legacy in hiphop culture has valued it at extremely high prices. Also notably widely used in rural America, particularly in the same poor, coal-mining Appalachia.
 
Have you heard of the agent where instead of dimethylamine, the last step of the amitriptyline synthesis is performed with norpethidine?

Davis, M. A., Herr, F., Thomas, R. A., Charest, M.-Paule. (July 1967). "New Psychotropic Agents. VIII. 1 Analogs of Amitriptyline Containing the Normeperidine Group". Journal of Medicinal Chemistry. 10 (4): 627–635. doi:10.1021/jm00316a024.

The background patent is for the corresponding benzhydryl compound (lacking the 2C bridge). This agent was discovered to have a duration of above >6 hours and extremely safe therapeutic index:

Gustav Ehrhart, Leopold Ther, Hans-Georg Alpermann, & Heinrich Ott, US3426028 (1969 to Hoechst AG).
 
SeekingOblivion said:
“hiphop culture” 🤣
Click to expand...
are you disputing this or just a racial jab? promethazine+codeine syrup- "Texas Tea" - and its effects were a huge influence/inspiration to the sounds of texas 90s rap, and its use/abuse grew to become commonplace in hiphop/rap culture as a whole. its demand and popularity led to the eventual discontinuation of Actavis Prometh+codeine syrup a decade ago. I could elaborate on its popularity in bluegrass culture, but its relative significance/impact on popular culture is far lesser.

Hence why someone asking about promethazine might be given a dirty look- it's asking about a commonly known drug of abuse.

Apologies for getting off topic.
 
pcplease said:
are you disputing this or just a racial jab? promethazine+codeine syrup- "Texas Tea" - and its effects were a huge influence/inspiration to the sounds of texas 90s rap, and its use/abuse grew to become commonplace in hiphop/rap culture as a whole. its demand and popularity led to the eventual discontinuation of Actavis Prometh+codeine syrup a decade ago. I could elaborate on its popularity in bluegrass culture, but its relative significance/impact on popular culture is far lesser.

Hence why someone asking about promethazine might be given a dirty look- it's asking about a commonly known drug of abuse.

Apologies for getting off topic.
Click to expand...

It’s just a racial jab.
 
4DQSAR said:
I would be extremely careful in asscribing a specific action in the brain as the cause of clinical depression. I'm old enough to have seen dozens of mechanisms proposed. It may well be the case that like schizophrnaia, it's actually more than one illness that presents with the same set of symptoms.

Often we don't know if a given action is the cause OR is the result of something further upstream.

Certainly if animal models agree one one thing, it's that depression in man cannot be modelled in animals very well. Hence so many candidates that showed robust antidepressent action in animal models proved to be of little or no value in man.
Click to expand...

Scoplamine Is a full anticholinergic yet displays very potent antidepressant effects.
 
I have treatment resistant depression, I have tried TMS 2 times the second time was a waste of time. No benefits.
Nowadays I take Vyvanse and 20mg Dexamphetimine with Vraylar that acts as an antidepressant. Surprisingly stimulants work well with antidepressants especially if you are adhd
 
You must log in or register to reply here.
Top