Silicon Investor (SI) -- The First Internet Community

STOCKTALK

We've detected that you're using an ad content blocking browser plug-in or feature. Ads provide a critical source of revenue to the continued operation of Silicon Investor. We ask that you disable ad blocking while on Silicon Investor in the best interests of our community. If you are not using an ad blocker but are still receiving this message, make sure your browser's tracking protection is set to the 'standard' level.

Biotech / Medical : Sepracor-Looks very promising -- Ignore unavailable to you. Want to Upgrade?

To: Neuroguy who wrote (1795)	2/20/1999 9:19:00 AM
From: Alan Cole	Respond to of 10280

Celexa causes less sexual dysfunction then Prozac. While an isomer of Prozac may also cause less sexual dysfunction that its parent, the mew agent may not be better than Celexa. Now, the pharmaceutical industry looks for portions of large markets - e.g. 10% market penetration of the SSRI market may be plenty (such as Allegra maintaining a respectable portion of the non-sedating antihistamine market). Right now, though, I suspect that Celexa may be the preferred SSRI in most clinical situations.

To: Neuroguy who wrote (1795)	2/20/1999 12:24:00 PM
From: Biomaven	Read Replies (1) \| Respond to of 10280

Neuroguy, In the conference call following the Prozac deal, they mentioned that Prozac II seemed to have increased 5HT2A effect compared with Prozac. My guess is that ultimately you will be able to individualize a cocktail for a particular individual, and that combinations of more specific agents will be the ultimate treatment for many depressions, anxieties etc. Lilly of course is ideally placed to do this, perhaps in combination with SNAP, who have cloned many of the 5HT receptor subtypes. (Incidentally, Lilly and SNAP are working on a 5HT1F agonist for migraine.) Here's an abstract on the sexual dysfunction issue, and one on targeting different subtypes in anxiety: Int Clin Psychopharmacol 1998 Jul;13 Suppl 6:S9-14 Serotonin, serotonergic receptors, selective serotonin reuptake inhibitors and sexual behaviour. Olivier B, van Oorschot R, Waldinger MD Department of Psychopharmacology, Rudolf Magnus Institute for Neurosciences, Faculty of Pharmacy, Utrecht University, The Netherlands. The serotonergic system in the brain modulates many types of behavioural and physiological processes. An example of this modulatory function is seen with the selective serotonin reuptake inhibitors (SSRIs) which enhance serotonin transmission and influence mood, anxiety states, aggression, feeding and sexual behaviour. At present, 14 different serotonin receptors have been described and, although the function and localization of many of these receptors is becoming increasingly clear, much remains unknown. The SSRIs are intriguing drugs; by blocking presynaptic and somatodendritic serotonin transporters, they enhance serotonergic neurotransmission and thereby activate serotonin receptors. It is this effect which leads to the characteristic effects of the SSRIs. Theoretically, however, it appears possible that they may have differential effects on the various subpopulations of serotonin receptors. Differences between the SSRIs have recently been reported in males with rapid ejaculation; fluvoxamine, in contrast to other SSRIs, did not affect rapid ejaculation. What difference in the mechanism of action between the SSRIs is responsible for this differential profile? A conditioned taste aversion procedure has been used in mice to investigate the discriminatory stimuli (cues) of fluvoxamine and fluoxetine. It appeared that the discriminatory stimulus of fluvoxamine is primarily mediated via 5-hydroxytryptamine (HT)1A receptors, whilst that of fluoxetine is primarily mediated via 5-HT2C receptors. Both types of receptors have been implicated in depression and it is conceivable that different SSRIs have intrinsic activity at these receptors. Investigations are now ongoing to determine whether this differential mechanism of action also applies to the other SSRIs and whether there are differences between the SSRIs with respect to their effect on sexual behaviour in rodents. Psychiatr Clin North Am 1995 Dec;18(4):895-909 Future directions in anxiolytic pharmacotherapy. Kunovac JL, Stahl SM Clinical Neuroscience Research Center, University of California, San Diego, USA. It seems that psychopharmacology may be well on its way toward the goal of developing new anxiolytic drug(s) that are fast acting and free from the unwanted effects associated with the traditional benzodiazepines. Several specific candidates exist, based upon rational targeting of neurotransmitter receptors shown to be linked to the neurobiology of anxiety. Thus, partial agonists at the benzodiazepine receptor, such as alpidem, abecarnil, and bretazenil, have highly promising preclinical profiles, and some useful preliminary results in clinical testing of anxiety disorder subjects. Neurosteroids are another interesting set of pharmacologic agents that target the benzodiazepine receptor, have a preclinical anxiolytic profile, and now need to be tested in clinical populations. Targeting of various serotonin (5HT) receptor subtypes is a very active area of current research for novel anxiolytic agents. 5HT3 antagonists may have an anxiolytic profile, but clinical results are still preliminary and need more validation. Of considerable interest is the idea of developing new drugs that act at 5HT1A, 5HT2A, or 5HT2C receptors. It has even been proposed that simultaneous targeting of both 5HT2A and 5HT1A receptors could result in robust anxiolytic agents that will have more immediate onset of action than currently available 5HT1A receptor acting drugs. Neuropeptide receptor agonists and antagonists with anxiolytic properties may represent one of the most striking new classes of potential anxiolytic drugs, but this is an emerging field that still requires considerably more systematic clinical testing. Nevertheless, preclinical studies as well as early clinical studies suggest that at least three neuropeptide receptors are provocative targets for novel anxiolytic agents: namely antagonists for CCK-B receptors, antagonists for CRF receptors, and agonists for neuropeptide Y receptors. Rational development of new pharmacologic agents based upon targeting receptors for those neurotransmitters that regulate the neurobiology of anxiety promises to bring forth a number of exciting therapeutic agents for the treatment of anxiety disorders in the future. --------------- Peter

To: Neuroguy who wrote (1795)	2/21/1999 11:08:00 AM
From: John Metcalf	Read Replies (1) \| Respond to of 10280

Thanks for the corrections, and additional information, Neuroguy and Peter. If I have the terminology correct, the 5HT receptor domain consists of fourteen known serotonin receptors. As Peter posted, some drugs primarily affect certain receptors; and all SSRI's increase general serotonin levels. And, as Neuroguy says, there is cross-reactivity such that more than one receptor can be affected by a given molecule. The point is not pedantic, because it points to _how_ one makes better psychoactive drugs. Some day, psychiatrists may order lab (or other) diagnostic work to determine which points within the domain should be stimulated/inhibited. Within this group are receptors linked to feeding, sleep, sexual activity, etc. It seems very likely that "cross reactivity" is the cause of some unwanted effects. More selective molecules, with better diagnostics supporting their use, can lead to focused treatment with fewer unintended effects. It also seems likely that chiral approaches can narrow the effect of a given drug, because of the cross-reactivity that occurs with existing ones.