This article explores some of the social and clinical issues facing the many different kinds of gay and lesbian families that are becoming increasingly visible in the United States. Research findings are discussed that dispel popularly held myths and stereotypes concerning these families, gays and lesbians as parents, and their children. Clinical vignettes are presented to illustrate issues often encountered in the consulting room, some unique to gay and lesbian families and some common to all families.

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All of the optical isomers of the muscarinic antagonists 3-(1-azabicyclo[2.2.2]octyl) alpha-hydroxy-alpha,alpha-diphenylacetate (3-quinuclidinyl benzilate, QNB, 1) 3-(1-azabicyclo[2.2.2]octyl) xanthene-9-carboxylate (3-quinuclidinyl xanthene-9-carboxylate, QNX, 2), and 3-(1-azabicyclo[2.2.2]ocytl) alpha-hydroxy-alpha-phenylpropionate (3-quinuclidinyl atrolactate, QNA, 3) were prepared and studied in binding and functional assays. In all instances the esters of (R)-1-azabicyclo[2.2.2]octan-3-ol (3-quinuclidinol) had greater affinity for the M1 and M2 subpopulations of muscarinic acetylcholine receptors (M-AChRs) than did their S counterparts. The enantiomers of QNB (1), QNX (2), and QNA (3) in which the alcoholic portion of the muscarinic antagonists had the S absolute stereochemistry were more selective for the M1-AChRs. This selectivity was modulated by the nature and, in the case of QNA, the chirality of the acid portion. The most potent isomer in the series was (R)-QNB. In the QNA series the diastereoisomer with the absolute R configuration of the alcohol (a) and the R configuration of the acid (b) was the most potent in both binding and functional assays whereas (Sa,Rb)-QNA was the most selective for the M1 subtype of M-AChRs. In fact, the latter diastereomer was as potent and selective as pirenzepine for M1-AChRs.

1-Azabicyclo[2.2.2]oct-3-yl alpha-hydroxy-alpha-(1-iodo-1-propen-3-yl)- alpha-phenylacetate (IQNP, 1), is a highly selective ligand for the muscarinic acetylcholinergic receptor (mAChR). There are eight stereoisomers in the racemic mixture. The optical isomers of alpha-hydroxy-alpha-phenyl-alpha-(1-propyn-3-yl)acetic acid were resolved as the alpha-methylbenzylamine salts, and the optical isomers of 3-quinuclidinol were resolved as the tartrate salts. The E and Z isomers were prepared by varying the reaction conditions for the stannylation of the triple bond followed by purification utilizing flash column chromatography. In vitro binding assay of the four stereoisomers containing the (R)-(-)-3-quinuclidinyl ester demonstrated that each isomer of 1 bound to mAChR with high affinity. In addition, (E)-(-)-(-)-IQNP demonstrated the highest receptor subtype specificity between the m1 molecular subtype (KD, nM, 0.383 +/- 0.102) and the m2 molecular subtype (29.6 +/- 9.70). In vivo biodistribution studies demonstrated that iodine-125-labeled (E)-(-)-(+)-1 cleared rapidly from the brain and heart. In contrast, iodine-125-labeled (E)-(-)-(-)-, (Z)-(-)-(-)-, and (Z)-(-)-(+)-1 have high uptake and retention in mAChR rich areas of the brain. It was also observed that (E)-(-)-(-)-IQNP demonstrated an apparent subtype selectivity in vivo with retention in M1 (m1, m4) mAChR areas of the rain. In addition, (Z)-(-)-(-)-IQNP also demonstrated significant uptake in tissues containing the M2 (m2) mAChR subtype. These results demonstrate that the iodine-123-labeled analogues of the (E)-(-)-(-)- and (Z)-(-)-(-)-IQNP isomers are attractive candidates for single-photon emission-computed tomographic imaging of cerebral and cardiac mAChR receptor densities.