Derivatives of fentanyl, 3-methylfentanyl, sufentanil, and lofentanil, possessing chemo- or photoaffinity functionalities, were synthesized as potential affinity reagents for the opiate receptor. Opiate receptor binding constants (IC50) were determined in competition experiments with [3H]naloxone and [3H]naltrexone. Affinity-labeling experiments were generally unsuccessful, although some irreversible attachment was achieved with alpha-diazoamide 17 and aryl azide 23.

Several novel approaches have been investigated for the synthesis of the LTD4/E4 antagonist LY290154. Significant improvements to the discovery route were first made by using an indoline nucleophile instead of an indolyl anion in the key substitution step. An alternative approach, introducing the 7-chloroquinoline moiety in the latest stages of the synthesis was then demonstrated. Interestingly, the pivotal intermediate of this latter route was also obtained in a one-pot process following a Katritzky methodology. Finally, an asymmetric synthesis offering significant advantages over the enantioselective route reported by McKillop was demonstrated.

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Solubilization of dopamine receptors, in a native form, was first achieved in our laboratory using dog striatum and the mild detergent digitonin [l-3]. These results were confirmed by another group in both dog and human brain [4f. However, earlier attempts to solubilize dopamine receptors from rat striatum were ~s~essfui~ even though a similar experimental procedure was used [3,5]. Although the binding properties of dopamine receptors in striatal membrane preparations were identical in both animals, the discrepancy between the data from rat and dog remained unexplained [3], This study was undertaken to solve the problem.The results show that the solubilized dopamine receptors from rat striatum are masked by a high number of non-specific but displaceable spiperone binding sites. These binding sites have been already described in membrane preparations as non-stereospecific or spirod~anone sites (cf. Gg.2) [6,7]. The use of a compound which is s~uct~a~y related to spiperone, but is inactive on dopamine receptors enabled us to determine and characterize solubilized dopamine receptors from the rat striatum, by means of the charcoal assay method. 2, Materials and methodsWistar rats were decapitated, mongreI dogs and cats were anaesthetized with pentobarbital; their brains were dI~ected~ut and homogenized in 0.25 M ice-cold sucrose. After preparation of the microsomal fraction f8], which may be kept at -16"C, the extraction was performed at 0°C with 1% digitonin