Methyllycaconitine analogues have mixed antagonist effects at nicotinic acetylcholine receptors

David Barker; Diana H.S. Lin; Jane E. Carland; Cindy P.Y. Chu; Mary Chebib; Margaret A. Brimble; G. Paul Savage; Malcolm D. McLeod

doi:10.1016/j.bmc.2005.04.054

Methyllycaconitine analogues have mixed antagonist effects at nicotinic acetylcholine receptors

David Barker, Diana H.S. Lin, Jane E. Carland, Cindy P.Y. Chu, Mary Chebib, Margaret A. Brimble, G. Paul Savage, Malcolm D. McLeod^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

64 Citations (Scopus)

Abstract

Bicyclic analogues of methyllycaconitine (MLA), such as 12, have been synthesised that incorporate the C1-OMe substituent present in the natural product. Electrophysiology experiments using Xenopus oocytes expressing nicotinic acetylcholine receptors (nAChRs) were conducted on these analogues and a related tricyclic analogue 2. The most potent compound, 2, was an antagonist at all receptors studied but displayed different antagonist effects at each receptor subtype. This study more clearly defines the biological effects of MLA analogues at nAChRs and demonstrates that these analogues are not selective ligands for the α7 nAChR subtype.

Original language	English
Pages (from-to)	4565-4575
Number of pages	11
Journal	Bioorganic and Medicinal Chemistry
Volume	13
Issue number	14
DOIs	https://doi.org/10.1016/j.bmc.2005.04.054
Publication status	Published - 15 Jul 2005
Externally published	Yes

Access to Document

10.1016/j.bmc.2005.04.054

Cite this

@article{38efcad4a60f4ea1a271e0abf0f8168e,

title = "Methyllycaconitine analogues have mixed antagonist effects at nicotinic acetylcholine receptors",

abstract = "Bicyclic analogues of methyllycaconitine (MLA), such as 12, have been synthesised that incorporate the C1-OMe substituent present in the natural product. Electrophysiology experiments using Xenopus oocytes expressing nicotinic acetylcholine receptors (nAChRs) were conducted on these analogues and a related tricyclic analogue 2. The most potent compound, 2, was an antagonist at all receptors studied but displayed different antagonist effects at each receptor subtype. This study more clearly defines the biological effects of MLA analogues at nAChRs and demonstrates that these analogues are not selective ligands for the α7 nAChR subtype.",

author = "David Barker and Lin, {Diana H.S.} and Carland, {Jane E.} and Chu, {Cindy P.Y.} and Mary Chebib and Brimble, {Margaret A.} and Savage, {G. Paul} and McLeod, {Malcolm D.}",

year = "2005",

month = jul,

day = "15",

doi = "10.1016/j.bmc.2005.04.054",

language = "English",

volume = "13",

pages = "4565--4575",

journal = "Bioorganic and Medicinal Chemistry",

issn = "0968-0896",

publisher = "Elsevier Ltd.",

number = "14",

}

TY - JOUR

T1 - Methyllycaconitine analogues have mixed antagonist effects at nicotinic acetylcholine receptors

AU - Barker, David

AU - Lin, Diana H.S.

AU - Carland, Jane E.

AU - Chu, Cindy P.Y.

AU - Chebib, Mary

AU - Brimble, Margaret A.

AU - Savage, G. Paul

AU - McLeod, Malcolm D.

PY - 2005/7/15

Y1 - 2005/7/15

N2 - Bicyclic analogues of methyllycaconitine (MLA), such as 12, have been synthesised that incorporate the C1-OMe substituent present in the natural product. Electrophysiology experiments using Xenopus oocytes expressing nicotinic acetylcholine receptors (nAChRs) were conducted on these analogues and a related tricyclic analogue 2. The most potent compound, 2, was an antagonist at all receptors studied but displayed different antagonist effects at each receptor subtype. This study more clearly defines the biological effects of MLA analogues at nAChRs and demonstrates that these analogues are not selective ligands for the α7 nAChR subtype.

AB - Bicyclic analogues of methyllycaconitine (MLA), such as 12, have been synthesised that incorporate the C1-OMe substituent present in the natural product. Electrophysiology experiments using Xenopus oocytes expressing nicotinic acetylcholine receptors (nAChRs) were conducted on these analogues and a related tricyclic analogue 2. The most potent compound, 2, was an antagonist at all receptors studied but displayed different antagonist effects at each receptor subtype. This study more clearly defines the biological effects of MLA analogues at nAChRs and demonstrates that these analogues are not selective ligands for the α7 nAChR subtype.

UR - http://www.scopus.com/inward/record.url?scp=20444447505&partnerID=8YFLogxK

U2 - 10.1016/j.bmc.2005.04.054

DO - 10.1016/j.bmc.2005.04.054

M3 - Article

SN - 0968-0896

VL - 13

SP - 4565

EP - 4575

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

IS - 14

ER -

Methyllycaconitine analogues have mixed antagonist effects at nicotinic acetylcholine receptors

Abstract

Access to Document

Other files and links

Fingerprint

Cite this