A Biotech Bash - Recs and Wrecks Message Board

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Biotech / Medical : A Biotech Bash - Recs and Wrecks

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To: r. peter Dale who wrote (78)	8/29/1997 1:50:00 AM
From: Miljenko Zuanic	of 171

Rick: Because I was hopeing that NeuroInvestment will respond to yours questions (he stated that in Sep. will release SIBI analysis) I didn't want to effect thread based on how he love me. By layman and IMO: 1. Few things related to drugs should be consider at any CNS-disorder : a. Fast onset of the action, as confirmation that molecula readily cross BBB and reach target site, b. Relative fast plasma clearing time of drugs and metabolite, to stable molecules or its metabolite can multiple potential side effects by accumulation (for CNS this is in pico-grams or lower), c. It is desire that molecule (structure) be simple as posible (at the some time selective), structure complesity increase posibility of the undisaer binding property. d. Brain is super-fine self-balanced biochemical fectory, and any intruder have more than one effect. d. There are no non-toxic drug. Only more or less toxic. 2. SIB-1508Y: Facts that drug is active for dopamine relase by cateholamine stimulation (released by subtipe NAChR) and unknown(?) nicotinic acetycholine sub-receptor is not bad unles: a. Acetylcholine level (not cateholamine) are elevated for long time and cumulative nature. Demage to pre- and post-synapse? Also, consequence will be to reduced dose (to limit acetylcholine level) wich will reduce positive dopamine release. b. The question is why cateholamine stimulation of D1 and D2 receptor is not in proportion of the acetylcholine activity? There are posibility that motor-function effects will be shaded by cognitive effects. ncbi.nlm.nih.gov ncbi.nlm.nih.gov To answer on this and other (?) question Sibia is conducting additional monkey study. By structure SIB-1805Y is similar to 53 series; NICOTINIC AChR-subtype receptors. It apears that , like SIB-1765F, it is more potent (~few 1000 fold) toward (-)nicotine displace than DA release. Botom line: PD disease is motor-function disorder and any drug needs to adress this problem first Luck of this activity apriory eliminate drug. Is the secundary effects of the NAChR agonist proper answer to problem? mz

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