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article request: diphenhydramine structure-activity relationship

wungchow

Bluelighter
Joined
Dec 12, 2006
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nyc
Anyone have any articles with comprehensive analysis of the structure-activity relationships of ethanolamine and related antihistamines?

i'm trying to design a short-acting sedating antihistamine, with an elimination half-life of between 2-4 hours.
 
There is a document that can be found online that's about Antihistamines.
It's called hist_antihis.pdf.
It contains everything you need to know about Antihistamines history, pharmacology, and chemistry (structures, derivatives, etc...)

There's a chapter about Ethanolamines and simple Diphenhydramine derivative (Methyldiphenhydramine, Chlorodiphenhydramine, Bromodiphenhydramine).

I know nothing about chemistry, but I think it explains how such or such modification on the Ethanolamine general structure can lead to stronger derivatives of Diphenhydramine.

P.S. as I can't find the document online, and can't upload it on Bluelight (the size is too big, it's a pdf), I uploaded it to my FTP and sent you the link.
 
protovack - the half-life of diphenhydramine in healthy adults is usually around 6-8 hr.

by comparison ambien's is 1.5-2.4


jason - thanks a lot, appreciate it
 
I guess if you increase the number of polar groups which aid removal and metabolism (reducing half-life) you make it far less likely to enter the brain and be a useful sleep aid.

Possibly why there are no short acting anti-histamine sleep aids? (although someone might know of one I don't and I know hepatic metabolism is far more complicated than just polar and non polar elements)

Also anti-histamines tend to have many other low potency pharmacological effects (e.g promethazine is something like a 1/10 th potency of chlorpromazine as anti-psychotic) which is fine left alone but I guess if you start changing functional groups even in small ways the result could quickly be a entirely different compound.

I think the first SSRI was derived from an anti-histamine...
http://en.wikipedia.org/wiki/Zimelidine
 
Reminisant B said:
I guess if you increase the number of polar groups which aid removal and metabolism (reducing half-life) you make it far less likely to enter the brain and be a useful sleep aid.

Possibly why there are no short acting anti-histamine sleep aids? (although someone might know of one I don't and I know hepatic metabolism is far more complicated than just polar and non polar elements)

Also anti-histamines tend to have many other low potency pharmacological effects (e.g promethazine is something like a 1/10 th potency of chlorpromazine as anti-psychotic) which is fine left alone but I guess if you start changing functional groups even in small ways the result could quickly be a entirely different compound.

I think the first SSRI was derived from an anti-histamine...
http://en.wikipedia.org/wiki/Zimelidine

I think the first generation of SSRI antidepressants (such as prozac) are all antihistamine derived -- the previous tricyclic antidepressants had antihistamine and anticholingenic activity.
 
Reminisant B said:
I think the first SSRI was derived from an anti-histamine...

Yes, and that's Chlorpheniramine (Chlorphenamine), the nasty antihistamine in Coricidin triple C....

"Chlorphenamine has antidepressant properties, inhibiting reuptake of the neurotransmitter serotonin. Based on this knowledge, the Swedish company Astra AB was able to derive the first marketed selective serotonin reuptake inhibitor, zimelidine, from chlorphenamine."
(from wikipedia)
 
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