Systemic administration of 5-HT2C receptor agonists attenuates muscular hyperalgesia in reserpine-induced myalgia model
submitted by papidapi 9 hours ago
Fibromyalgia is a prevalent musculoskeletal disorder characterized by chronic widespread pain that significantly reduces quality of life in patients. Due to the lack of consistently effective treatment, the development of improved therapies for treating fibromyalgia is necessary. As dysfunction of serotonergic analgesic control appears to be involved in the pathophysiology of fibromyalgia, the present study explored the potential of 5-HT2C receptor agonists as novel therapies for treating this disease. Three 5-HT2C receptor agonists (lorcaserin, vabicaserin and YM348) that have been suggested to be useful in the treatment of several central nervous system diseases, including obesity and schizophrenia, were used. The effect of systemic administration of these agents on the muscular hyperalgesia that develops in the reserpine-induced myalgia (RIM) rat, a putative animal model of fibromyalgia, was investigated. RIM rats exhibited decreased muscle pressure thresholds. Microdialysis experiments showed that the concentration of serotonin (5-HT) in the spinal cord of RIM rats was significantly lower than that of controls. Lorcaserin (0.3–3mg/kg p.o.), vabicaserin (0.3–3mg/kgs.c.) and YM348 (0.03–0.3mg/kg p.o.) recovered the muscle pressure threshold. The effect of lorcaserin was reversed by the pretreatment with SB242084, a 5-HT2C receptor antagonist. Our findings demonstrate that 5-HT2C receptors play a critical role in muscular hyperalgesia in RIM rats and suggest that 5-HT2C receptor agonists have therapeutic potential for treating chronic pain in patients with fibromyalgia although clinical extrapolation remains to be a future challenge.
Why is this relevant and exciting for ARNA? It relates to the very real possibility that physicians will initially start some of their overweight, fibromyalgia patients on belviq. They might then see that these same patients report improvements in there fibromyalgia symptoms. Eventually they then start expanding their use of belviq to their thin fibromyalgia patients. This is called off label use of an FDA approved product and is a common and legal. Eventually, ARNA may do additional studies to modify the label, but this is not necessary to see millions of dollars of additional sales. What you need to understand is that this same process is likely to occur with other related conditions such as prediabetes/ metabolic syndrome, schizophrenia, smoking cessation, etc where pre clinical studies have already been shown to benefit from 5HTC2 receptor stimulation.
Eisai has based their billion dollar sales prediction for belviq on at least one label expansion. This news highlights the potential markets of this drug which most of wall street and the analysts are just not reporting. The people who understand this now are going to make alot of money in the long run IMHO. GLTA.
Sentiment: Strong Buy
The science above is hard for me to follow, but with no real cure, this is freat news. I have Fibro, and although not life threatening, it is a hard thing to deal with. For some people it can be debilitating. I take 2 differnet meds each day, but still have some rough days (About 2 per week). Where is the abpve study from?
Great post fgz_fgz
I was just at a medical talk last night - the topic being the disservice we've done patients by haphazardly prescribing opiods for chronic non-malignant pain. A good portion of the talk focused on fibromyalgia and while we have medications for this, they're not very effective.
I treat many patients with fibromyalgia using both medications and physical modalities. This is very welcome news and I will keep my eye out for further developments. Thank you for the post!
More evidence every day that specific receptor interactions as a basis for developing more precise targeted drugs is an area of tremendous potential..... remember when genetics and genome coding started to really get going? The scientific basis is infolding here today and consider how this could work in conjunction with genetic biotechnology. Arena was and is a recognized leader in this area.... Belviq marketing is an engine to finance expanded development of their IP.
all imo, of course
Don't have any of those things. Most of the time it occurs as a trauma to the body whether physical or emotional. In my case, it was a surgery and I developed it 6 wks. after the surgery. Nothing out there right now that really helps. This is exciting for all of the many fibro patients out here. Thanks Sauve9 and for FGZ for posting.
Sentiment: Strong Buy
Pharmacology Biochemistry and Behavior
Available online 18 April 2013
Yukinori NagakuraCorresponding author contact information, E-mail the corresponding author,
Pharmacology Research Labs, Drug Discovery Research, Astellas Pharma, Inc.
Sentiment: Strong Buy