Article: 7766 of alt.support.depression.medication From: "Joe D." Newsgroups: alt.support.depression.medication,alt.support.attn-deficit,sci.med.pharmacy,sci.med References: Subject: Re: Why cant they develope more Dopamine reuptake innhibitors? Lines: 47 MIME-Version: 1.0 Content-Type: text/plain; charset="iso-8859-1" Content-Transfer-Encoding: 7bit X-Priority: 3 X-MSMail-Priority: Normal X-Newsreader: Microsoft Outlook Express 6.00.2800.1106 X-MimeOLE: Produced By Microsoft MimeOLE V6.00.2800.1106 Message-ID: <5OILa.145$4U3.82385@news.uswest.net> Date: Sun, 29 Jun 2003 14:24:16 -0700 NNTP-Posting-Host: 63.226.197.16 X-Trace: news.uswest.net 1056921857 63.226.197.16 (Sun, 29 Jun 2003 16:24:17 CDT) NNTP-Posting-Date: Sun, 29 Jun 2003 16:24:17 CDT Path: news.meer.net!sea-read.news.verio.net!dfw-artgen!sjc-peer.news.verio.net!news.verio.net!HSNX.atgi.net!newsfeed.frii.net!newsfeed.frii.net!140.99.99.194.MISMATCH!newsfeed1.easynews.com!easynews.com!easynews!feed.news.qwest.net!news.uswest.net.POSTED!not-for-mail Xref: archive.mv.meer.net alt.support.depression.medication:7766 alt.support.attn-deficit:1502 sci.med.pharmacy:566 sci.med:4493 "gabatril" wrote in message news:eadac0ae.0306291026.562f517e@posting.google.com... > I think the med pharmacy should have focused more on developing > dopaminergic AD`s than focus so much on serotonin and > Noradrenalin,developed more drugs like wellbutrin that could affect > Dopamine even more Whether and to what degree Wellbutrin affects dopamine is somewhat complex. See http://www.preskorn.com/columns/0001.html There's also a potential addiction or abuse problem with dopamine-based drugs. Supposedly this is why the dopamine-based AD Amineptine (Survector) was taken off the market. That said, the biological cause of some common SSRI side effects is fairly well understood. Namely it's stimulation of the 5HT2a serotonin receptor. Some drugs such as Remeron block that receptor, providing the AD effect of increased serotonin without the sexual and other side effects. Unfortunately Remeron also activates the H1 (histamine) receptor causing drowsiness and weight gain. It would seem the fastest path to an improved conventional AD would be to blockade the 5HT2a receptor and not activate anything else like H1. You'd have a regular SSRI without most of the side effects. This is so obvious I must conclude the drug companies are working on this. It's increasingly obvious the actual mechanism of action for any AD is not at the neurotransmitter level. Rather modulating the neurotransmitter initiates a multi-step biochemical cascade, the final stage of which causes the antidepressant effect. Identifying what this cascade is and designing drugs to target the final stage is a top research priority. It's possible such drugs could work faster, have fewer side effects, and cure a broader range of problems than existing drugs. One of these pathways involves Substance P, which Merck targeted with their experimental AD MK-869. They had some good results, but other studies showed it was less effective than hoped. I think they're re-doing those tests. Another suggested pathway involves stress->corticotropin releasing hormone-> ACTH->cortisol, resulting in damage to the hippocampus. Some new drugs are CRF antagonists, to try and block this. Here are some drugs under development: http://www.abpi.org.uk/publications/publication_details/targetDepression/section6.asp -- Joe D.