[125I]IPH, an epibatidine analog, binds with high affinity to neuronal nicotinic cholinergic receptors.
An analog of epibatidine (EB) was synthesized with an iodine atom in the 2 position of the pyridyl ring. This analog, (+/-)-exo-2-(2-iodo-5-pyridyl)-7-azabicyclo[2.2.1]heptane (IPH), as well as its two stereoisomers, displayed high affinity for neuronal nicotinic receptors; therefore, radioiodinated IPH, [125I]IPH, was synthesized with specific radioactivities consistently > 1000 Ci/mmol, and its properties as a radioligand for neuronal nicotinic receptors were evaluated. The characteristics of [125I]IPH binding in tissue homogenates appeared to be virtually identical to those reported for [3H]epibatidine binding; but the high specific radioactivity of [125I]IPH greatly facilitated measurements of nicotinic receptors in tissues with relatively low receptor densities and/or where tissues are in limited supply. Autoradiography with [125I]IPH provided clear localization of nicotinic receptors in brain and adrenal gland after film exposure times of < or = 2 days. We conclude that [125I]IPH will be a very useful radioligand for the study of neuronal nicotinic receptors in brain and in peripheral ganglia.
Dávila-García
M I
MI
Department of Pharmacology, Georgetown University School of Medicine, Washington, DC 20007, USA.
Musachio
J L
JL
Perry
D C
DC
Xiao
Y
Y
Horti
A
A
London
E D
ED
Dannals
R F
RF
Kellar
K J
KJ
D000818:Animals; D001345:Autoradiography; D001665:Binding Sites; D001921:Brain / Q000378:metabolism*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000378:metabolism*; D008297:Male; D018722:Nicotinic Agonists / Q000378:metabolism*; D011725:Pyridines / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000378:metabolism*; D013237:Stereoisomerism
C107078:2-(2-iodo-5-pyridyl)-7-azabicyclo(2.2.1)heptane; D019086:Bridged Bicyclo Compounds, Heterocyclic; D018722:Nicotinic Agonists; D011725:Pyridines; D011978:Receptors, Nicotinic; C082748:epibatidine