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Biotech / Medical : momo-T/FIF -- Ignore unavailable to you. Want to Upgrade?

To: Biotech Jim who wrote (10763)	7/22/2016 3:02:16 PM
From: tuck	Read Replies (1) \| Respond to of 12215

CARA: Preclinical data re abuse potential: >>INVESTIGATION OF THE DISCRIMINATIVE AND REINFORCING PROPERTIES OF THE K-OPIOID RECEPTOR AGONIST CR845 IN RATS Smith SL, RenaSci Ltd, BioCity, Nottingham, NG1 1GF sharon.smith@renasci.co.uk Spencer R(1), Menzaghi F(1), Gosden J(2), Slater N(2), Holland SJ(2), Slade J(2), Heal DJ(2) (1) Cara Therapeutics, Inc., 1 Parrott Drive, Shelton CT 06484; (2) RenaSci Ltd, BioCity, Nottingham NG1 1GF CR845 is a peripherally-acting ?-opioid receptor agonist being developed to treat pain and pruritus. CR845 has no activity at µ- or d-opioid receptors. These studies investigated whether CR845 generalised to the discriminative cue elicited by the centrally acting mixed ?/s-receptor agonist and µ-receptor partial agonist, (-)pentazocine or substituted as a positive reinforcer in an intravenous self administration (IVSA) experiment in heroin-maintained rats. Lister-Hooded female rats were trained to discriminate (-) pentazocine (5mg/kg ip) from saline. Butorphanol, a ?/µ opioid agonist, was selected as the reference comparator. Test drugs were tested 15min after iv injection. Results are reported as mean±SD percentage generalisation to the (-)pentazocine cue. Sprague-Dawley, male, rats were trained to self administer heroin (0.015mg/kg/inj) on a FR5 schedule. After saline extinction, CR845 and (-)pentazocine were evaluated in separate groups of rats in 2 hour sessions. IVSA results are reported as mean±SEM. Drug-discrimination was validated by the dose dependent generalisation of iv (-)pentazocine (0.017 0.5 mg/kg,iv) to the training cue (17.7±8.9% to 75.8±8.2% [n=6]). The reference comparator, butorphanol (0.001–0.25 mg/kg iv), dose- dependently generalised to (-)pentazocine (17.1±11.7% to 76.6±17.5% [n=6/7]). CR845 (0.05, 0.125, 0.25, 0.5 mg/kg iv) generalised to saline at the lowest dose, (23.6±10.5% [n=7]) and partially generalised to (-) pentazocine at all other doses (35.4±20.2% [n=7], 31.0±17.9% [n=7], 34.5±10.1% [n=7], respectively) with no evidence of dose-dependence. Heroin-maintained IVSA in all rats (15.83±0.85 inj/session, n=13) that was signi cantly greater (p<0.001) than saline (3.65±0.37 inj/session, n=13). None of the doses of CR845 (0.001, 0.005, 0.025 or 0.125mg/kg/inj) maintained rates of IVSA at a level signi cantly greater than saline and all doses were signi cantly lower than heroin. (-)Pentazocine (0.03, 0.1 or 0.245mg/kg/inj) maintained IVSA at signicantly greater levels than saline. (-)Pentazocine and butorphanol both generalised fully to the cue elicited by ip (-)pentazocine validating the model for detecting drugs with µ- and ?-agonist properties. CR845 produced low-level, non-dose-dependent, partial generalisation to (-)pentazocine. This result is consistent with the fact that CR845 is a potent ?-opioid receptor agonist with poor brain penetration. CR845 did not serve as a positive reinforcer in heroin-maintained rats. The reference comparator, (-)pentazocine, substituted for heroin in the model and served as a positive reinforcer across a range of doses. If these results translate into man, they predict that CR845 is unlikely to be recreationally abused by humans. Study funded by Cara Therapeutics Inc.<< Abstract presented at British Association of Psychopharmacology Good for almost 20% today. This is resisting some formatting efforts, but is readable. Cheers, Tuck

To: Biotech Jim who wrote (10763)	8/5/2016 10:41:26 AM
From: tuck	Read Replies (1) \| Respond to of 12215

CARA: off around 10% after earnings on a good day for the casino. I listened to the CC and didn't hear anything to account for the drop. The last question dealt with the reduced dosing in the post-op trial, and the answer was that vaguer than what you posted here. Basically that the compound was very potent at the receptor, and that they had seen signals with these doses in prior trials. So much for "Cowen comments" effect. Has a time line slipped somewhere? TIA & Cheers, Tuck