steroid-alkaloids as pgp-inhibitors

[morphiquet]

i just found a quite exciting abstract discussing the efficiacy of tomatidine and other steroid-alkaloids as chemosensitizers. they write that tomatidine is comparable to verapamil in its potency to block the drug-transporting pgp's.

now, those of you who have always dreamed of kicking loperamid through their bbb, will know of what i'm speaking.
tomatidine is more than easily to obtain and its toxicity is bearable.

here's the abstract:

Lavie Y, Harel-Orbital T, Gaffield W, Liscovitch M.
Inhibitory effect of steroidal alkaloids on drug transport and multidrug resistance in human cancer cells.
Anticancer Res. 2001 Mar-Apr;21(2A):1189-94.

 

[raybeez]

i just found a quite exciting abstract discussing the efficiacy of tomatidine and other steroid-alkaloids as chemosensitizers. they write that tomatidine is comparable to verapamil in its potency to block the drug-transporting pgp's.

Lavie Y, Harel-Orbital T, Gaffield W, Liscovitch M.
Inhibitory effect of steroidal alkaloids on drug transport and multidrug resistance in human cancer cells.
Anticancer Res. 2001 Mar-Apr;21(2A):1189-94.

Do you know if this effect is due to some type of pgp-antagonism, achievable with a single dose? Or is it a gene regulation / receptor down-regulation effect typical of steroid drugs?

Also:
This experiment was done with tissue cultured tumor cells, not in vivo. There's not really any way of knowing if these compounds would have the same effect on the human pgp's of interest if they were to be ingested...

 

[morphiquet]

yea, of course the in vivo-experiments are up to us.
if i had the silver bullet to my otc-opioid, maybe i wouldn't uncover that so easily.

but i'm lokking forward to next summer, when the tomatoes start growing

edit: the text says definitely that these alkaloids act as direct inhibitors, not as manipulators of gene-expression.