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Absorption of Polypeptides?

Jabberwocky

Jabberwocky

Frumious Bandersnatch
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Would a polypeptide that is active via intramuscular injection also be active intranasally, intrarectally, or sublingually?

Oxytocin
IGF-1
Vasopressin
Desmopressin
 
Vasopressin is active intranasally, and I think oxytocin might be as well.

However other peptide/protein drugs like human growth hormone and bremelanotide have to be injected, so its a bit unreliable, probably depends on molecular weight and other factors like how easily metabolised it is (some polypeptides are tougher than others I'm sure).

I'm pretty sure none of them are active sublingually, and I've never heard of anyone trying rectal administration...

Also the South American frog species known as "sapo", Phyllomedusa bicolour, produces opioid agonist peptides in its skin, and the traditional method of taking them is to burn yourself and then rub the frogslime into the burn. So people have managed to administer peptide drugs without needles, its just a bit more difficult.
 
so...your in pain...you find your frog slime...you cause yourself more pain...then slab on some frog slime...
 
mad_scientist said:
Vasopressin is active intranasally, and I think oxytocin might be as well.
Click to expand...

Yes, oxytocin is active intranasally. Intranasal activity is determined by size (with smaller peptides being more active than smaller ones) and probably also amino acid sequence.
 
mad_scientist said:
However other peptide/protein drugs like human growth hormone and bremelanotide have to be injected, so its a bit unreliable, probably depends on molecular weight and other factors like how easily metabolised it is (some polypeptides are tougher than others I'm sure).
Click to expand...

Also depends on the energy minimum of its native state, ie how easily it denatures. Proteins (bigger peptides) are more fragile and depend more crucially on their tertiary structure for activity.
 
My point being it depends on lots of factors that cannot easily be extrapolated, the things already stated and others like the induction of a immune system response, stability at various pHs, ability to cross membranes, ability to cross the BBB, half-life in the blood due to various other macromolecules (proteases) or things like macrophages hunting them out, etc. etc.

There's really only one way to find out.

As mentioned for the intranasal, the use of permeabilizing agents that open up the tight? junctions between the cells greatly increases absorption for all molecules (new coke cutting agents anyone?) so some drugs get through the nose no problem while others will never make it, especially most (if not all) peptides larger than 50 AA.
 
Could these permeabilizing agents allow oral administration of an otherwise inactive peptide (such as IGF-1)?

Are these types of permeabilizing agents approved in FDA studies or are they unresearched?

And, out of curiousity, has anybody tried oxytocin in a large psychoactive dose? Possibly in combination with tryptamine hallucinogens?
 
1. Yes, but only via buccal administration (the cheeks), it wouldn't help if you swallowed it.
2. Yes, and, don't quote me on this, available in some drugs already, perhaps nasal spray drugs?
3. no :)
 
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