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Biotech / Medical : Neurocrine Biosciences (NBIX) -- Ignore unavailable to you. Want to Upgrade?

To: NeuroInvestment who wrote (578)	4/7/2000 2:04:00 AM
From: Miljenko Zuanic	Read Replies (1) \| Respond to of 1834

Rick, Harry, 1. I do not read the some. 16 months ago NBIX/Janssen have back-up compound (from some class) ready. Back-up compound is also covered in DuPont patent and licenses in three way agreement. However, three party agreement also mentioned that NBIX/Janssen are entering new period of the R&D collaboration where new class compounds and lead will be explored. Last news mentioned this new collaboration as source for new compounds, so I am assuming that next candidate will be from new program and (NBIX) library, not from the some class as R121. 2. Based on what I think that R121 is (which class), I did found similar compounds on market or in development, but none with hepatic toxicity. So, it may be derivatization related, and not necessary true for any analogue. 3. NBIX is short on current patents, so it is hard to tell what are this new class compounds. However, NBIX/Janssen were not the only one who failed with first gen. CRF-R1 antagonist because of the toxicity. It may turn out that NBIX proprietary programs/compounds are top-notch, but without further detail I will be cautious about. Miljenko

To: NeuroInvestment who wrote (578)	6/22/2000 9:28:00 PM
From: Miljenko Zuanic	Read Replies (1) \| Respond to of 1834

Any comment on this anxiety rat model will be appreciated. Does NBIX use some model? Miljenko Effects of the CRF(1) receptor antagonist, CP 154,526, in the separation-induced vocalization anxiolytic test in rat pups. Kehne JH, Coverdale S, McCloskey TC, Hoffman DC, Cassella JV Neurogen Corporation, 35 Northeast Industrial Road, 06405, Branford, CT, USA [Record supplied by publisher] CRF(1) receptor antagonists have been proposed as novel pharmacological treatments for depression, anxiety and stress disorders. The primary goal of the present study was to evaluate the effects of the CRF(1) receptor antagonist, CP 154,526, in the separation-induced vocalization (SIV) model of anxiety. Nine- to 11-day-old rat pups were separated from their litter and the effects of intraperitoneally administered test compounds on the elicited ultrasonic vocalizations were measured. Side-effect potential was assessed using a modifed inclined plane test ('time on an inclined plane', or TIP), and using negative geotaxis. SIV was reduced by CP 154,526 at doses that did not affect TIP or negative geotaxis, a profile like that of the 5-HT(1A) partial agonist buspirone. The benzodiazepine anxiolytic, diazepam, decreased SIV but also produced significant side effects at one to three-fold higher doses. Additional pharmacological characterization of SIV demonstrated anxiolytic-like effects of the atypical antipsychotic, clozapine, but not the typical antipsychotic, haloperidol, and of the serotonin reuptake inhibitor, zimelidine, but not the norepinephrine reuptake inhibitor, desipramine. In summary, the data support the conclusion that selective CRF(1) receptor antagonists may have utility in anxiety and stress disorders. The data further support the use of separation-induced vocalizations for identifying mechanistically diverse compounds with anxiolytic actions in man.