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A high-affinity, nonpeptide radioligand for the CRHR1 was synthesized and showed distribution in rat brain consistent with CRHR1 using in vitro autoradiography. This is the first nonpeptide radiotracer combining high affinity and appropriate lipophilicity that penetrates the blood−brain barrier and hence has the potential to be used for PET imaging studies. In vivo visualization of changes in the CRH1 receptor or its occupancy would further the understanding of the pathophysiology of stress related diseases.

A species of Besnoitia from naturally infected rabbits from Argentina was propagated experimentally in mice, gerbils, rabbits, cats, and cell cultures. Cats fed tissue cysts from rabbits shed oocysts with a prepatent period of nine to 13 days. Sporulated oocysts were infective to gerbils, rabbits, outbred Swiss Webster and interferon gamma gene knockout mice. Bradyzoites were infective orally to gerbils and cats. Tachyzoites were successfully cultivated and maintained in vitro in bovine monocytes and African green monkey kidney cells. Schizonts were seen in the lamina propria of the small intestine of cats fed tissue cysts; the largest ones measured 52×45 μm. Schizonts were also present in mesenteric lymph nodes, livers, and other extra-intestinal organs of cats fed tissue cysts. Oocysts were 10–14×10–13 μm in size. This rabbit-derived species of Besnoitia resembled B. darlingi of the North American opossum, Didelphis virginiana with an opossum-cat cycle, but it was not transmissible to D. virginiana, and B. darlingi of opossums was not transmissible to rabbits. Based on biological, serological, antigenic, and molecular differences between the rabbit and the opossum Besnoitia, a new name, B. oryctofelisi is proposed for the parasite from domestic rabbits from Argentina.

The synthesis, biological, and pharmacological evaluations of 14β-O-phenylpropyl-substituted morphinan-6-ones are described. The most striking finding of this study was that all of the compounds from the novel series of differently N-substituted 14β-O-phenylpropylmorphinans acted as powerful opioid agonists. Even with N-substituents such as cyclopropylmethyl and allyl, which are usually associated with distinct antagonist properties, only agonists were obtained. Compared to morphine, the N-cyclopropylmethyl derivative 15 showed considerably increased potency in the in vivo assays in mice (600-fold in the tail-flick assay, 60-fold in the paraphenylquinone writhing test, and 400-fold in the hot-plate assay). Remarkably, most of the new ligands were nonselective and exhibited binding affinities in the subnanomolar range at opioid receptors (μ, κ, δ), with the N-propyl derivative 19 displaying the highest affinity for the μ-receptor (Ki = 0.09 nM).

A series of 4-[2-[bis(4-fluorophenyl)methoxy]ethyl-1-benzylpiperidines were examined for their ability to bind to the dopamine transporter (DAT), the serotonin transporter (SERT), and the norepinephrine transporter (NET). Binding results indicated that the presence of an electron-withdrawing group in the C4-position of the N-benzyl group is beneficial for binding to the DAT. Several analogues have been identified with high affinity for the DAT, up to 500-fold selectivity over the SERT and about 170-fold selectivity over the NET in binding and uptake inhibition assays.

14-Alkoxy analogues of naltrindole and naltriben differently substituted in positions 5 and 17 and at the indole nitrogen (compounds 28−44) have been synthesized in an effort to enhance the δ potency and/or δ selectivity and in order to further elaborate on structure−activity relationships of this class of compounds. Introduction of a 14-alkoxy instead of the 14-hydroxy group present in naltrindole resulted in somewhat lower δ binding affinity, while in many cases (compounds 31, 34, 37, 40, 41, 44, HS 378) the δ receptor selectivity was considerably increased. An ethoxy group in position 14 is superior to other alkoxy groups concerning δ affinity and selectivity (34, 41, 42, 44, HS 378). In [³⁵S]GTPγS binding, compounds 34, 41, and HS 378 exhibited about one-tenth the antagonist potency of naltrindole at δ opioid receptors while their δ antagonist selectivity was considerably higher. 17-Methyl-substituted compounds 35 and 44 were found to be pure δ receptor agonists in this test.

A series of 4-[2-[bis(4-fluorophenyl)methoxy]ethylpiperidines were examined for their ability to bind to the dopamine transporter (DAT), the norepinephrine transporter, and the serotonin transporter (SERT). In particular, the role of the N-substituent on affinity and selectivity for the DAT was probed. 4-[2-[Bis(4-fluorophenyl)methoxy]ethyl-1-(2-naphthylmethyl)piperidine was found to possess subnanomolar affinity (Ki = 0.7 nM) and good selectivity for the DAT (SERT/DAT = 323).