H1-receptor antagonists - Why are they so cool? And what still needs to be learned?

[Changa707]

Seems like all the "old-school" first generation antihistamines out there have a great number of off-label indications...and as an opioid user, I find some of them to be great potentiators...adding an aspect to the high that is very meditative and surreal (especially with the anticholinergics like atropine and benztropine).
I have self-experimented with Equanil, Orphenadrine citrate, Diphenhydramine, Scopolamine, and Benztropine. Keep in mind, I am taking threshold doses of benztropine and scopolamine (250 micrograms)...which still leaves me with visual disturbances, but adds a very unique dissociation to the codeine and temazepam which I combine alongside my antihistamines/anticholinergics.

Orphenadrine seems to pack quite a punch at 100 mg, but I prefer the 0.25 mg benztropine because it causes less mouth dryness and has more prominent CNS depressing effects. Both of these substances seem to induce very mild "Shadow people" sensations...but it's minor.

So lets get into the pharmacology a little bit...since this is the neuroscience/pharmacology thread. I'm not trained in medical school or anything, but I consider myself well-read to some extent...I'm just curious about the potential off-label uses of these drugs I have been talking about. Particularly Orphenadrine and Benztropine. They are both closely related to diphenydramine, orphenadrine moreso. But I feel much less hangover and depressive side effects with orphenadrine than I do with diphenhydramine. I have found that orphenadrine has a sleuth of positive effects for me...it increases mood, produces a sublte sense of calm...yet allows me to be productive and even provides anxiety relief. Interestingly enough, I find orphenadrine to cause insomnia is some instances...it does not really make me sleepy, but gives me energy (kinda like the oxycodone of antihistamines). Same this with Benztropine, which I find to have simutaneously sedating and stimulating effects which add to the floaty feeling I get when nodding on opioids.

Only downside with Bentropine at only 0.25 mg is that the antihistamine effects are mediocre at best, but better than nothing at all. I'd say the benztropine is more like a weak cocaine high with nastier side effects (though I haven't even ventured into higher doses yet, but I know that benztropine is related to tropane alkaloids...so it must share some similarities.

Going off topic here sorry, i'm a bit high...restoril is kicking in alongside the 90 mg codeine. Go back 1.5 hours, I dosed 0.25 mg benztropine and 300 mg gabapentin. The synergy is taking place, and I feel that the benztropine is adding a new dimension of dissociation to the experience, that I quite enjoy (but I could imagine that taking a high dose of this substance on it's own would be unpleasant to say the least).

Hey, but in the end...it's really hard to tell what drug is giving what effect when you are on 4 substances at once (Temazepam, Codeine, Tylenol, Benztropine, & Gabapentin). I can say that the temazepam is the most noticeable, but I can also notice the dissociative effects of the Benztropine quite well. The opiate w/d from smoked heroin are 100% at bay, and I feel great (this is at T+48 hours since last toke).

Anyhow, as bad as Benztropine can be at high doses (not that I have taken high doses, but heard bad experiences)...it can have great benefits in low doses, 0.25 seems to do the trick...next time i'll try 0.5 mg.

So for all you pharmacologists and neuroscientists out there...do you think we will see more off-label uses for first-generation antihistamines and anticholinergics in the future? These drugs seem to be very effective, yet can prove to have undesirable effects even at clinical dosages (especially the anticholinergics). What is it about this H1 receptor that makes it have such a high affinity for binding and having strong CNS depressing effects?
Why do these antihistamines and anticholingeric have such dose-dependent effects, and unpredictability? I have heard of people hallucinating from scopolamine, atropine and others at medicinal dosages.

I know I'm asking a lot here, and am rather disorganized in my presentation...mind me for being under the influence. But I am genuinely curious about this peculiar class of drugs that are H1-receptor antagonists. Maybe there just is this nostalgia surrounding the old school muscle relaxers and antihistamines...i'm talking good old' Promethazine, Carisoprodol, Meprobamate, Orphenadrine, Diphenhydramines....they all seem to work well combined with opioids, though i'm not sure Carisoprodol or Meprobamate has antihistamine effects. But what they do all share in common is that they were developed between 1950s and 1960's. These drugs were very popular when they came out, and still are extremely popular today (except Miltown, which is quite a memorable tradename)!

So big question here....what is the future of H1-receptor antagonists in today's medicine? What don't we yet fully understand about the action of H1-receptor antagonists (pharmacologically speaking)?

 

[Black]

I have found that orphenadrine has a sleuth of positive effects for me...it increases mood, produces a sublte sense of calm...yet allows me to be productive and even provides anxiety relief.

i wouldn't necessarily call that off-label indications. hydroxyzine is a first-generation antihistaminic and is widely prescribed for that purpose. many doctors prescribe it instead of benzos nowadays...
they probably choose hydroxyzine over the others because it lacks affinity for the acetylcholine receptors thus eliminating the anticholinergic side effects.

 

[Changa707]

Wow Black, this is quite interesting...doctors in Europe are prescribing Vistaril as a replacement for benzodiazepines in the treatment of anxiety? I mean it makes sense to me...Vistaril is certainly less liable to abuse, though it's quite strange considering the nature of that drug (as far as i'm aware it's similiar to thorazine?).

Great way to treat anxiety huh, just turn the person into a zombie...since zombies don't have feelings. Haha, sorry i'm talking shit here...I have never tried Mellaril or Vistaril, so I can't speak for their effects.

 

[sekio]

Hydroxyzine is actually much less zombifying than you'd expect. The use of hydroxyzine isn't old either, I know docs in the US were using it in the 70s/80s, good old Elron Haggard took it IV for elevated thetan levels

 

[Changa707]

Hydroxyzine is actually much less zombifying than you'd expect. The use of hydroxyzine isn't old either, I know docs in the US were using it in the 70s/80s, good old Elron Haggard took it IV for elevated thetan levels

Wow, I thought this thread wouldn't go anywhere...but what you mentioned is interesting. Well first off, I would like to point out that I mistakenly associated Vistaril (an antihistamine) with Mellaril (Major Tranquilizer). Although i'm not sure how related/dissimilar they are chemically & pharmacologically?

What sort of sparked my interest in the H-1 histamines was doing research on Promethazine...which introduced me to Thorazine...which introduced me to an article on SDSU about the use of Thorazine in the Peoples Temple, under the command of the infamous Jim Jones.

I'm not even going to try to understand "Thetan levels"...but sounds like something a cultish group like scientology would happily embrace. Hydroxyzine was one of the drug's used in the "Nurses Office" by Jonestown physician Larry Schacht...presumably as a means of controlling dissenters. But if you look at the actual medical/pharmacy records of Jonestown released through the FOIA - Document J-1 http://jonestown.sdsu.edu/wp-content/uploads/2013/10/J-1.pdf - it shows that Thorazine was the drug of choice for that purpose in Jonestown. Hydroxyzine seems to have only been used a few times, probably for genuine purposes. I was under the impression that Thorazine and Hydroxyzine were basically very similar...but i'm guessing now that Hydroxyzine is actually much less of an antipsychotic than Thorazine?

Please take a look at that PDF, and check out the article - http://jonestown.sdsu.edu/?page_id=40232 on SDSU regarding the use of Thorazine at Jonestown. It seems that in Jonestown they used a hell of a lot of Thorazine at the "Nurses Office", which makes me wonder what is so unique about this drug that made it the drug of choice for essentially "Zombifying" those brave souls that chose to dissent? I'm guessing that they used this drug for it's qualities as a major tranquilizer? But then you read the logs and they really didn't use much of their Haldol but quite a bit of Mellaril (less so than Thorazine, however). Seems like those two would have been equally well suited at "zombifying" the dissenters, just seems peculiar that they didn't use any Haldol (which they had about 500 mg of). Could there be a practical reason for this?

Document J-1 navigation (just to make it easier to find the relevant logs)

Hydroxyzine - pg. 12-13
Thorazine - pg. 20-24
Haldol - pg. 28-30
Mellaril - pg. 54-57