U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

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Dextromilnacipran (1R, 2S/F2696) is an enantiomer of milnacipran, a serotonin/norepinephrine (5-HT/NE) reuptake inhibitor. Dextromilnacipran is pharmacologically less active as compared with racemic mixture and levomilnacipran (1S, 2R/F2695).
Duloxetine (brand names Cymbalta, Yentreve, and in parts of Europe, Xeristar or Ariclaim) is indicated for the acute and maintenance treatment of major depressive disorder (MDD), as well as acute management of generalized anxiety disorder. Also used for the management of neuropathic pain associated with diabetic peripheral neuropathy, and fibromyalgia. Has been used in the management of moderate to severe stress urinary incontinence (SUI) in women. It is manufactured and marketed by Eli Lilly and Company. Duloxetine has not yet been FDA approved for stress urinary incontinence or for fibromyalgia. Duloxetine is a selective SNRI (selective serotonin-norepinephrine reuptake inhibitor). Duloxetine is a systemic drug therapy which affects the body as a whole. Known also under the code name LY248686, it is a potent dual reuptake inhibitor of serotonin (5-hydroxytryptamine, 5-HT) and norepinephrine (NE), possessing comparable affinities in binding to NE- and 5-HT transporter sites. It is a less potent inhibitor of dopamine reuptake.
Pregabalin, marketed under the brand name Lyrica among others. LYRICA is indicated for: Neuropathic pain associated with diabetic peripheral neuropathy (DPN) Postherpetic neuralgia (PHN); Adjunctive therapy for adult patients with partial onset seizures; Fibromyalgia; Neuropathic pain associated with spinal cord injury. It has been shown the clinical effects of pregabalin are likely due to direct and selective interactions with α(2)δ-1 and α(2)δ-2 subunits of voltage-gated calcium channels. While pregabalin is a structural derivative of the inhibitory neurotransmitter gamma aminobutyric acid (GABA), it does not bind directly to GABAA, GABAB, or benzodiazepine receptors, does not augment GABAA responses in cultured neurons, does not alter rat brain GABA concentration or have acute effects on GABA uptake or degradation. However, in cultured neurons prolonged application of pregabalin increases the density of GABA transporter protein and increases the rate of functional GABA transport. Pregabalin does not block sodium channels, is not active at opiate receptors, and does not alter cyclooxygenase enzyme activity. It is inactive at serotonin and dopamine receptors and does not inhibit dopamine, serotonin, or noradrenaline reuptake.
Status:
Investigational
Source:
NCT04614337: Phase 2 Interventional Completed Growth Hormone Deficiency
(2020)
Source URL:

Class (Stereo):
CHEMICAL (ABSOLUTE)



Ibutamoren (L-163,191 MK-0677) is a spiropiperidine agonist of the ghrelin receptor and a growth hormone secretagogue. Ibutamoren mimics the actions of growth hormone releasing peptide-6 to increase serum levels of serum insulin-like growth factor-I (IGF-I). Orally active Ibutamoren was being developed by Merck & Co. for a variety of indications, including fibromyalgia, muscle wasting/weakness in patients with chronic kidney disease, Alzheimer's disease and fractures.However, there has been no recent development reported or development has been discontinued for these indications.
Dolasetron is an antinauseant and antiemetic agent, which is approved as a mesylate salt under the brand name anzement for the prevention of nausea and vomiting associated with moderately emetogenic cancer chemotherapy, including initial and repeat courses; and for the prevention of postoperative nausea and vomiting. Dolasetron is a highly specific and selective serotonin 5-HT3 receptor antagonist. The serotonin 5-HT3 receptors are located on the nerve terminals of the vagus in the periphery and centrally in the chemoreceptor trigger zone of the area postrema. It is thought that chemotherapeutic agents produce nausea and vomiting by releasing serotonin from the enterochromaffin cells of the small intestine, and that the released serotonin then activates 5-HT3 receptors located on vagal efferents to initiate the vomiting reflex. This drug is not shown to have activity at other known serotonin receptors, and has low affinity for dopamine receptors. Dolasetron mesilate is rapidly reduced by carbonyl reductase to form its major pharmacologically active metabolite reduced dolasetron. In addition dolasetron was in the phase III clinical trials for the investigation, that intravenous using of dolasetron mesilate reduces pain intensity in patients with fibromyalgia.
Status:
Possibly Marketed Outside US

Class (Stereo):
CHEMICAL (ABSOLUTE)



D-ribose, a naturally occurring pentose carbohydrate, and a key component in the adenosine triphosphate (ATP) molecule. D-ribose was studied for congestive heart failure. In addition was discovered, that D-ribose significantly reduced clinical symptoms in patients suffering from fibromyalgia and chronic fatigue syndrome. Recently was published an article where were described, that d-Ribose reacted with the N-terminal valinyl residues of hemoglobin (Hb), thus producing glycated hemoglobin (HbA1c). It is known, that HbA1c is the most important marker of hyperglycemia in diabetes mellitus, which prompts future studies to explore whether D-ribose could also lead to diabetic complications.
Status:
Possibly Marketed Outside US
Source:
NCT01998620: Phase 4 Interventional Unknown status Hepatitis B
(2013)
Source URL:

Class (Stereo):
CHEMICAL (EPIMERIC)



S-Adenosylmethionine (often referred to as SAMe) is a methyl donor and a cofactor for enzyme-catalyzed methylations, including catechol O-methyltransferase (COMT) and DNA methyltransferases (DNMT). Although present in all cells, it is concentrated in liver where 85% of all methylation reactions occur. SAM is anti-apoptotic in normal hepatocytes and normal colon epithelial cells but pro-apoptotic in liver human hepatocellular carcinoma (HCC), HepG2 cells and colon cancer cells. Because of structural instability, stable salt forms of SAM are required for its use as an oral drug. The commonly used salts: tosylate, butanedisulfonate, disulfate tosylate, disulfate ditosylate, and disulfate monotosylate. SAMe has been marketed in some European countries since the mid-1980s for the treatment of depression and for other medical conditions such as osteoarthritis (joint disease that causes joint pain and stiffness), fibromyalgia (widespread pain and stiffness). In addition, it is used to treat liver disease and migraine headaches. However, it is not formally approved in the UK for the treatment of depression, and in the USA, it is classified only as a dietary supplement. Some research suggests that it is more effective than placebo in treating mild-to-moderate depression and is just as effective as antidepressant medications without the side effects (headaches, sleeplessness, and sexual dysfunction). In addition, antidepressants tend to take 6 to 8 weeks to begin working, while It seems to begin more quickly. Researchers are not sure how SAMe works to relieve depression. But they speculate it might increase the amount of serotonin in the brain just as some antidepressants do. Many studies have examined injectable forms of SAMe, not oral supplements.
Status:
Possibly Marketed Outside US
Source:
Arcalion by Ammo, T.|Sakai, T.|Aizawa, T.|Fujihira, E.|Naganuma, A.
Source URL:

Class (Stereo):
CHEMICAL (ACHIRAL)


Sulbutiamine (isobutyryl thiamine disulfide) is a lipophilic derivative of thiamine. It is available over-the-counter in several countries either as a component of nutritional supplements or as a pharmaceutical preparation. Arcalion (Sulbutiamine) is prescribed as a treatment to help patients with a range of conditions such as asthenia, chronic fatigue, diabetes, hypothyroidism, renal disease, fibromyalgia, and depression (post partum). It remedies the symptoms of weakness by increasing focus, strength (both physical and mental), and energy, making you more alert, less lethargic, and more upbeat whilst also helping to stabilize sleeping patterns. In addition, this medication can also help a patient`s memory, and strengthen thinking processes. Some patient`s have even reported slight eyesight improvements. This product is also popular with athletes as a nutritional supplement as it is a vitamin compound which will not show up in competitive sports blood testing. It can help to achieve your maximum potential and replenish energy after strenuous activities, making it possible to maintain your edge. The presence of sulbutiamine in urinary doping control samples was monitored to evaluate the relevance of its use in sports. The motivating, confidence enhancing effects of sulbutiamine are thought to be related to its ability to enhance dopamine sensitivity. In animal models sulbutiamine has been shown to increase the number of dopamine binding sites (specifically D1) in the prefrontal cortex, this effect is achieved through reduction of dopamine release. Sulbutiamine could be best thought of as a dopamine modulator rather than a compound that directly inhibits or enhances the release of dopamine. Additionally sulbutiamine has been found to enhance memory, possibly by cholinergic transmission. Research indicates that high affinity choline uptake (HACU) was moderately increased in rodent brains following sulbutiamine consumption. However it should be noted the doses used were high (300 mg/kg).
Dextromilnacipran (1R, 2S/F2696) is an enantiomer of milnacipran, a serotonin/norepinephrine (5-HT/NE) reuptake inhibitor. Dextromilnacipran is pharmacologically less active as compared with racemic mixture and levomilnacipran (1S, 2R/F2695).