Eriksson_2012_J.Pharm.Pharmacol_64_1667

Reference

Title : In-vitro evaluation of the P-glycoprotein interactions of a series of potentially CNS-active Amaryllidaceae alkaloids - Eriksson_2012_J.Pharm.Pharmacol_64_1667
Author(s) : Eriksson AH , Ronsted N , Guler S , Jager AK , Sendra JR , Brodin B
Ref : J Pharm Pharmacol , 64 :1667 , 2012
Abstract :

OBJECTIVES: Drug compounds interacting with the blood-brain barrier efflux transporter P-glycoprotein (P-gp) might have limited access to brain tissue. The aim of the present study was to evaluate whether nine potentially CNS-active Amaryllidaceae alkaloids of the crinine, lycorine and galanthamine types interact with P-gp. METHODS: Alkaloids with inhibitory activity towards either the serotonin reuptake transporter or acetylcholinesterase, or both, were investigated using the calcein-AM efflux assay in Madin-Darby canine kidney cells transfected with human multidrug resistance transporter 1. KEY FINDINGS: Powelline and 6-hydroxycrinamine showed an interaction with P-gp, with IC50 values between 300 and 500 microM. 3-O-Acetylhamayne showed a weaker interaction, with an IC50 value above 3 mM. Epibuphanisine, lycorine, 1-epi-deacetylbowdenisine, papyramine and galanthamine all showed weak or no interaction with P-gp. There was no observed correlation between alkaloid type and P-gp interaction. CONCLUSIONS: Structurally similar compounds such as crinine and epibuphanisine showed very different P-gp interactions, highlighting the difficulty in predicting P-gp interactions. Epibuphanisine has previously shown activity in the serotonin reuptake transporter assay and may therefore serve as a lead for serotonin reuptake transporter active compounds. The most potent compound in the acetylcholinesterase assay, the marketed drug compound galanthamine (Reminyl), showed no interaction with P-gp.

PubMedSearch : Eriksson_2012_J.Pharm.Pharmacol_64_1667
PubMedID: 23058055

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Citations formats

Eriksson AH, Ronsted N, Guler S, Jager AK, Sendra JR, Brodin B (2012)
In-vitro evaluation of the P-glycoprotein interactions of a series of potentially CNS-active Amaryllidaceae alkaloids
J Pharm Pharmacol 64 :1667

Eriksson AH, Ronsted N, Guler S, Jager AK, Sendra JR, Brodin B (2012)
J Pharm Pharmacol 64 :1667