mimicking endolipids to carry enkephalinase inhibitors

[leungkachong]

Just a plea for information concerning the mimicking of endolipids (triglyceride esters type thingmabobs) for carriers as someone mentioned the use of such methods w/ thiorphan (an enkephalinase inhibitor), providing a superior agent, that exhibits naloxone-reversible analgesia. The lipidish compounds were apparently not perticularily good substrate for the receptor, and the drug the compound is derived from (or some fragment metabolite) is most likely being released at/near the site.

 

[leungkachong]

*sigh*, well at least i was able to track down the article (pubmed was messed when i was searching).

Lambert DM, Mergen F, Berens CF, Poupaert JH, Dumont P. "Synthesis and pharmacological properties of 2-[S-acetylthiorphan]-1,3- diacylaminopropan-2-ol derivatives as chimeric lipid drug carriers containing an enkephalinase inhibitor." Pharm Res. 1995 Feb;12(2):187-91.

Any related research?

 

[BilZ0r]

I still don't understand the question man. So you're saying there are endogenous lipids, which inhibit enkephalinase or some other opioid destroyer?

Or are you after endogenous lipids which help non-BBB permiable drugs to get into your noggen?

Either way, here is the full version of the article.

...and here is a list of articles citing that article.

1. Lambert DM
Rationale and applications of lipids as prodrug carriers
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES 11: S15-S27 Suppl. 2 OCT 2000
Times Cited: 9
Full Text View full text from the publisher Elsevier Science
2. Thorre K, Sarre S, Twahirwa E, et al.
Effect of L-tryptophan, L-5-hydroxytryptophan and L-tryptophan prodrugs on the extracellular levels of 5-HT and 5-HIAA in the hippocampus of the rat using microdialysis
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES 4 (4): 247-256 JUN 1996
Times Cited: 5
Full Text View full text from the publisher Elsevier Science
3. Anderson BD
Prodrugs for improved CNS delivery
ADVANCED DRUG DELIVERY REVIEWS 19 (2): 171-202 MAY 22 1996
Times Cited: 9
Full Text View full text from the publisher Elsevier Science
4. Lambert DM, Scriba GKE, Poupaert JH, et al.
Anticonvulsant activity of ester- and amide-type lipid conjugates of glycine and N-benzyloxycarbonylglycine
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES 4 (3): 159-166 MAY 1996
Times Cited: 4
Full Text View full text from the publisher Elsevier Science
5. Abbott NJ, Romero IA
Transporting therapeutics across the blood-brain barrier
MOLECULAR MEDICINE TODAY 2 (3): 106-113 MAR 1996

Hope that was of some help. I figured you could probably get both of the things I've offered, but it couldn't hurt.

 

[leungkachong]

I meant about drug delivery. They seemed to give the impression that these PTG's are vectored more specifically than simply to float across the BBB. Not only that, I'm not sure if you read the article, but there's some really interesting mentions of the differences in chain length/structure, which had pharmacological significace. However, the parent carrier compounds themselves were not perticularily strong at the receptor. Thiorphan released? A pro-drug metabolite fragment of the carrier? Differences in speed and/or path of metabolism of the PTG's from moiety substitutions?

 

[Tri-nity]

Dont mean to hijack the thread but what substances can be taken to make leporamide(Ammodium ad) cross the BBB better?