Alterations of the muscarinic cholinergic (mACh) receptors in the striatum of the MPTP-induced parkinsonian model in mice: In vitro quantitative autoradiographical analysis

Autoradiographic study on dopamine uptake sites and their correlation with dopamine levels and their striata from patients with Parkinson disease, Alzheimer disease, and neurologically normal controls

“…Muscarinic binding sites were determined by incubation for 120 min at 20°C with 1 nM [ 3H]QNB (32.9 Ci/mmol, New England Nuclear) in 50 mM Tris-HCI, pH 7.6; atropine (1 µM) was used as the competitive inhibitor (Mizukawa et al, 1987).…”

Synthesis and biodistribution of iodine-125-labeled 1-azabicyclo[2.2.2]oct-3-yl .alpha.-hydroxy-.alpha.-(1-iodo-1-propen-3-yl)-.alpha.-phenylacetate. A new ligand for the potential imaging of muscarinic receptors by single photon emission computed tomography

“…In addition, the vinyl iodide group allows incorporation of the iodine in a metabolically stable position,18 as we have previously demonstrated with a variety of radiopharmaceuticals including fatty acids,20 most recently, spiroperidol analogues.30 We report the synthesis, in vitro evaluation, and the radiolabeling of IQNP (3) with iodine-125, as well as the biodistribution, in vivo displacement studies, and competitive binding studies with this new ligand.…”

“…Since complete separation of the two isomers by flash column chromatography could not be achieved, the isomeric mixture was thus carried to the next step without further separation. When temperatures higher than 80 °C were employed in the stannylation sequence the product yield was decreased due to the subsequent decomposition of 6. Compound 6 was then treated with iodine in chloroform to afford an approximately 1:1 mixture of (E)-and (Z)l-azabicyclo[2.2.2] octyl-3-yl a-hydroxy-a-(1-iodo-1-propen-3-yl)-a-phenylacetate (3). Although TLC analysis indicated the presence of a single isomer, high-pressure liquid chromatographic (HPLC) and NMR analysis of 3 indicated an approximate equal mixture of the (E)-and (Z)-isomers.…”

“…In this paper we report the synthesis, in vitro, and in vivo evaluation of a newQNB analogue, l-azabicyclo[2.2.2]oct-3-yl a-hydroxy-a-(l-iodo-l-propen-3-yl)-a-phenylacetate (IQNP, 3), in which one of the phenyl rings of QNB is replaced by an iodopropenyl group. Earlier reports of various analogues of 1 have indicated that changes could be made in place of one of the phenyl rings without greatly affecting the affinity for the m-AChR receptor.17 These studies have shown that analogues in which a phenyl ring is replaced with a cyclopentyl, cyclohexyl, or n-butyl group are almost equipotent with QNB.…”

“…

l-Azabicyclo[2.2.2]oct-3-yl a-hydroxy-a-(l-iodo-l-propen-3-yl)-a-phenylacetate (IQNP,3), an analogue of QNB in which a phenyl ring has been replaced with an iodopropenyl substituent, was prepared and evaluated in vitro and in vivo for m-AChR selectivity and specificity. High specific activity ['25]IQNP ([1251]-3) was synthesized in greater than 60% yield utilizing an electrophilic iododestannylation reaction with hydrogen peroxide for the oxidation of iodide.

…”