List of investigational analgesics

Last updated

This is a dynamic list and may never be able to satisfy particular standards for completeness. You can help by adding missing items with reliable sources.

This is a list of investigational analgesics , or analgesics that are currently under development for clinical use but are not yet approved. Chemical/generic names are listed first, with developmental code names, synonyms, and brand names in parentheses.

Contents

This list was last comprehensively updated in June 2017. It is likely to become outdated with time.

Opioid receptor modulators

Sodium channel blockers

Calcium channel blockers

TRP channel modulators

Cannabinoid receptor modulators

Nerve growth factor inhibitors

Others

See also

Related Research Articles

<span class="mw-page-title-main">Cannabigerol</span> Minor cannabinoid

Cannabigerol (CBG) is a non-psychoactive cannabinoid and minor constituent of cannabis. It is one of more than 120 identified cannabinoids found in the plant genus Cannabis. The compound is the decarboxylated form of cannabigerolic acid (CBGA), the parent molecule from which other cannabinoids are biosynthesized.

The orexin receptor (also referred to as the hypocretin receptor) is a G-protein-coupled receptor that binds the neuropeptide orexin. There are two variants, OX1 and OX2, each encoded by a different gene (HCRTR1, HCRTR2).

<span class="mw-page-title-main">Nalfurafine</span> Antipruritic drug

Nalfurafine is an antipruritic that is marketed in Japan for the treatment of uremic pruritus in individuals with chronic kidney disease undergoing hemodialysis. It activates the κ-opioid receptor (KOR) and is potent, selective, and centrally active. It was the first selective KOR agonist approved for clinical use. It has also been dubiously referred to as the "first non-narcotic opioid drug" in history.

<span class="mw-page-title-main">NESS-0327</span> Chemical compound

NESS-0327 is a drug used in scientific research which acts as an extremely potent and selective antagonist of the cannabinoid receptor CB1. It is much more potent an antagonist, and more selective for the CB1 receptor over CB2, than the more commonly used ligand rimonabant, with a Ki at CB1 of 350fM (i.e. 0.00035nM) and a selectivity of over 60,000x for CB1 over CB2. Independently, two other groups have described only modest nanomolar CB1 affinity for this compound (125nM and 18.4nM). Also unlike rimonabant, NESS-0327 does not appear to act as an inverse agonist at higher doses, instead being a purely neutral antagonist which blocks the CB1 receptor but does not produce any physiological effect of its own.

<span class="mw-page-title-main">Agonist-antagonist</span> Type of drug

In pharmacology the term agonist-antagonist or mixed agonist/antagonist is used to refer to a drug which under some conditions behaves as an agonist while under other conditions, behaves as an antagonist.

A cannabinoid receptor antagonist, also known simply as a cannabinoid antagonist or as an anticannabinoid, is a type of cannabinoidergic drug that binds to cannabinoid receptors (CBR) and prevents their activation by endocannabinoids. They include antagonists, inverse agonists, and antibodies of CBRs. The discovery of the endocannabinoid system led to the development of CB1 receptor antagonists. The first CBR inverse agonist, rimonabant, was described in 1994. Rimonabant blocks the CB1 receptor selectively and has been shown to decrease food intake and regulate body-weight gain. The prevalence of obesity worldwide is increasing dramatically and has a great impact on public health. The lack of efficient and well-tolerated drugs to cure obesity has led to an increased interest in research and development of CBR antagonists. Cannabidiol (CBD), a naturally occurring cannabinoid and a non-competitive CB1/CB2 receptor antagonist, as well as Δ9-tetrahydrocannabivarin (THCV), a naturally occurring cannabinoid, modulate the effects of THC via direct blockade of cannabinoid CB1 receptors, thus behaving like first-generation CB1 receptor inverse agonists, such as rimonabant. CBD is a very low-affinity CB1 ligand, that can nevertheless affect CB1 receptor activity in vivo in an indirect manner, while THCV is a high-affinity CB1 receptor ligand and potent antagonist in vitro and yet only occasionally produces effects in vivo resulting from CB1 receptor antagonism. THCV has also high affinity for CB2 receptors and signals as a partial agonist, differing from both CBD and rimonabant.

<span class="mw-page-title-main">Samidorphan</span> Opioid antagonist

Samidorphan is an opioid antagonist that in the form of olanzapine/samidorphan is used in the treatment of schizophrenia and bipolar disorder. Samidorphan reduces the weight gain associated with olanzapine. Samidorphan is taken by mouth.

A receptor modulator, or receptor ligand, is a general term for a substance, endogenous or exogenous, that binds to and regulates the activity of chemical receptors. They are ligands that can act on different parts of receptors and regulate activity in a positive, negative, or neutral direction with varying degrees of efficacy. Categories of these modulators include receptor agonists and receptor antagonists, as well as receptor partial agonists, inverse agonists, orthosteric modulators, and allosteric modulators, Examples of receptor modulators in modern medicine include CFTR modulators, selective androgen receptor modulators (SARMs), and muscarinic ACh receptor modulators.

<span class="mw-page-title-main">Vixotrigine</span> Analgesic drug under development

Vixotrigine, formerly known as raxatrigine, is an analgesic which is under development by Convergence Pharmaceuticals for the treatment of lumbosacral radiculopathy (sciatica) and trigeminal neuralgia (TGN). Vixotrigine was originally claimed to be a selective central Nav1.3 blocker, but was subsequently redefined as a selective peripheral Nav1.7 blocker. Following this, vixotrigine was redefined once again, as a non-selective voltage-gated sodium channel blocker. As of January 2018, it is in phase III clinical trials for trigeminal neuralgia and is in phase II clinical studies for erythromelalgia and neuropathic pain. It was previously under investigation for the treatment of bipolar disorder, but development for this indication was discontinued.

Peripherally selective drugs have their primary mechanism of action outside of the central nervous system (CNS), usually because they are excluded from the CNS by the blood–brain barrier. By being excluded from the CNS, drugs may act on the rest of the body without producing side-effects related to their effects on the brain or spinal cord. For example, most opioids cause sedation when given at a sufficiently high dose, but peripherally selective opioids can act on the rest of the body without entering the brain and are less likely to cause sedation. These peripherally selective opioids can be used as antidiarrheals, for instance loperamide (Imodium).

<span class="mw-page-title-main">Fosdagrocorat</span> Chemical compound

Fosdagrocorat is a nonsteroidal but steroid-like selective glucocorticoid receptor modulator (SGRM) which was under development for the treatment of rheumatoid arthritis but was never marketed. It is the C2 dihydrogen phosphate ester of dagrocorat, and acts as a prodrug of dagrocorat with improved pharmacokinetics. The drug reached phase II clinical trials prior to the discontinuation of its development.

<span class="mw-page-title-main">RQ-00202730</span> Chemical structure

RQ-00202730 is a benzimidazole derived drug that acts as a potent and highly selective agonist for the CB2 cannabinoid receptor, with a Ki value of 19nM at CB2 and more than 4000x selectivity over CB1, though it also shows some activity as an antagonist of the unrelated 5-HT2B serotonin receptor. It has analgesic and antiinflammatory effects in animal studies, and was developed for the treatment of irritable bowel syndrome, but was ultimately discontinued from development following disappointing results in Phase II clinical trials.

References

  1. ↑ "Drug profile | Axelopran/oxycodone" . AdisInsight . Theravance Biopharma. 1 October 2021. Retrieved 29 October 2022.
  2. ↑ "Drug profile | Cebranopadol" . AdisInsight . Tris Pharma. 14 August 2022. Retrieved 29 October 2022.
  3. ↑ "Drug profile | Desmetramadol" . AdisInsight . Syntrix Biosystems. 5 October 2021. Retrieved 2 November 2022.
  4. ↑ "Drug profile | Lexanopadol" . AdisInsight . 20 August 2018. Archived from the original on 25 December 2018. Retrieved 2 November 2022.
  5. ↑ "Drug profile | Oxycodone/naltrexone" . AdisInsight . Elite Pharmaceuticals. 16 April 2021. Archived from the original on 14 November 2022. Retrieved 14 November 2022.
  6. ↑ "Drug profile | BIIB 095" . AdisInsight . Biogen. 7 May 2021. Archived from the original on 14 November 2022. Retrieved 14 November 2022.
  7. ↑ "Drug profile | CC 8464" . AdisInsight . Chromocell Corporation. 28 November 2019. Archived from the original on 15 March 2022. Retrieved 14 November 2022.
  8. ↑ "Drug profile | Cenobamate" . AdisInsight . SK biopharmaceuticals. 28 November 2019. Archived from the original on 14 November 2022. Retrieved 14 November 2022.
  9. ↑ Zaccara, Gaetano; Schmidt, D. (2017). "Antiepileptic Drugs in Clinical Development: Differentiate or Die?". Current Pharmaceutical Design . 23 (37). Bentham Science Publishers: 5593–5605. doi:10.2174/1381612823666170809100524. eISSN   1873-4286. ISSN   1381-6128. PMID   28799516. S2CID   3676340.
  10. ↑ Nakamura, Michiko; Shin, Hyewon; Jang, Il-Sung (26 April 2018). "Mechanism of Action of Cenobamate: Preferential Inhibition of the Persistent Sodium Current (P5.278)". Neurology . 90 (15 Supplement). doi:10.1212/WNL.90.15_supplement.P5.278. eISSN   1526-632X. ISSN   0028-3878. LCCN   55043902. OCLC   960771045. S2CID   80887455.
  11. ↑ "Drug profile | DSP 2230" . AdisInsight . Sumitomo Dainippon Pharma. 4 April 2022. Archived from the original on 14 November 2022. Retrieved 14 November 2022.
  12. ↑ "Drug profile | Funapide" . AdisInsight . Xenon Pharmaceuticals. 6 September 2022. Archived from the original on 14 November 2022. Retrieved 14 November 2022.
  13. ↑ "GDC 0276 - AdisInsight". adisinsight.springer.com.
  14. ↑ "GDC 0310 - AdisInsight". adisinsight.springer.com.
  15. ↑ "NKTR 171 - AdisInsight". adisinsight.springer.com.
  16. ↑ "PF 5089771 - AdisInsight". adisinsight.springer.com.
  17. ↑ "Ralfinamide - Newron Pharmaceuticals - AdisInsight". adisinsight.springer.com.
  18. ↑ "Tetrodotoxin - WEX Pharmaceuticals - AdisInsight". adisinsight.springer.com.
  19. ↑ "Vixotrigine - Biogen - AdisInsight". adisinsight.springer.com.
  20. ↑ "VX 150 - AdisInsight". adisinsight.springer.com.
  21. ↑ Nichols, Heather (19 July 2021). "Vertex Initiates Phase 2 Clinical Trial Program for VX-548 for the Treatment of Acute Pain". Vertex Pharmaceuticals (Press Release). Retrieved 14 November 2022. Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced that it has begun a Phase 2 proof-of-concept (POC) study in acute pain following bunionectomy surgery with the selective NaV1.8 inhibitor VX-548 and that it expects to commence a second Phase 2 study in acute pain following abdominoplasty surgery in the coming weeks.
  22. ↑ Cross, Ryan (31 March 2022). "Vertex's non-opioid painkiller shows promise in people recovering from surgery" . The Boston Globe . ISSN   0743-1791. OCLC   66652431. Archived from the original on 19 May 2022. Retrieved 14 November 2022. "There is an enormous need for novel non-opioid analgesics with no abuse liability," and Vertex's results are an "important advance," said Dr. Clifford J. Woolf, director of the F.M. Kirby Neurobiology Center and Boston Children's Hospital. It will be important for Vertex to determine whether the drug also works for patients with chronic pain, such as diabetic neuropathy and low back pain, "where the clinical need is highest," he added.
  23. ↑ Gou, Xiaoli; Yu, Xiaojuan; Bai, Dongdong; Tan, Bowei; Cao, Pingfeng; Qian, Meilin; Zheng, Xiaoxiao; Chen, Lei; Shi, Zongjun; Li, Yao; Ye, Fei; Liang, Yong; Ni, Jia (2021). "Pharmacology and Mechanism of Action of HSK16149, a Selective Ligand of α 2 δ Subunit of Voltage-Gated Calcium Channel with Analgesic Activity in Animal Models of Chronic Pain". Journal of Pharmacology and Experimental Therapeutics. 376 (3): 330–337. doi: 10.1124/jpet.120.000315 . PMID   33293377.
  24. ↑ "Capsaicin - Centrexion Therapeutics - AdisInsight". adisinsight.springer.com.
  25. ↑ "Capsaicin/Diclofenac - Boehringer Ingelheim - AdisInsight". adisinsight.springer.com.
  26. 1 2 "CMX 020 - AdisInsight". adisinsight.springer.com.
  27. ↑ "DWP 05195 - AdisInsight". adisinsight.springer.com.
  28. ↑ "GRC 6211 - AdisInsight". adisinsight.springer.com.
  29. ↑ "JNJ 38893777 - AdisInsight". adisinsight.springer.com.
  30. ↑ Manitpisitkul, Prasarn; Shalayda, Kevin; Russell, Lucille; Sanga, Panna; Solanki, Bhavna; Caruso, Joseph; Iwaki, Yuki; Moyer, John A. (10 November 2017). "Pharmacokinetics and Safety of Mavatrep (JNJ-39439335), a TRPV1 Antagonist in Healthy Japanese and Caucasian Men: A Double-Blind, Randomized, Placebo-Controlled, Sequential-Group Phase 1 Study". Clinical Pharmacology in Drug Development. 7 (7): 712–726. doi:10.1002/cpdd.413. eISSN   2160-7648. ISSN   2160-763X. PMID   29125703. S2CID   11755963.
  31. ↑ Manitpisitkul, Prasarn; Shalayda, Kevin; Russell, Lucille; Sanga, Panna; Williams, Yinka; Solanki, Bhavna; Caruso, Joseph; Moyer, John A. (2018). "Bioavailability and Pharmacokinetics of TRPV1 Antagonist Mavatrep (JNJ-39439335) Tablet and Capsule Formulations in Healthy Men: Two Open-Label, Crossover, Single-Dose Phase 1 Studies". Clinical Pharmacology in Drug Development. 7 (7): 699–711. doi:10.1002/cpdd.412. ISSN   2160-7648. PMID   29125700. S2CID   32666782.
  32. ↑ "NEO 6860 - AdisInsight". adisinsight.springer.com.
  33. ↑ "Parentide - DiverDrugs - AdisInsight". adisinsight.springer.com.
  34. ↑ "Resiniferatoxin - Sorrento Therapeutics - AdisInsight". adisinsight.springer.com.
  35. ↑ "SAR 115740 - AdisInsight". adisinsight.springer.com.
  36. ↑ "Tivanisiran - Sylentis - AdisInsight". adisinsight.springer.com.
  37. ↑ "Elcubragistat - Lundbeck A/S - AdisInsight". adisinsight.springer.com.
  38. ↑ "Synthetic cannabidiol - Benuvia Therapeutics/Radius Health - AdisInsight". adisinsight.springer.com.
  39. ↑ "Cannabidiol - ANANDA Scientific - AdisInsight". adisinsight.springer.com.
  40. ↑ "Cannabidivarin - GW Pharmaceuticals - AdisInsight". adisinsight.springer.com.
  41. ↑ "Dronabinol - Echo Pharmaceuticals - AdisInsight". adisinsight.springer.com.
  42. ↑ "Dronabinol buccal - IntelGenx - AdisInsight". adisinsight.springer.com.
  43. ↑ "Nabilone controlled release - AOP Orphan Pharmaceuticals - AdisInsight". adisinsight.springer.com.
  44. ↑ "ART 2713 - AdisInsight". adisinsight.springer.com.
  45. ↑ "Olorinab - Pfizer - AdisInsight". adisinsight.springer.com.
  46. ↑ "Fasinumab - Mitsubishi Tanabe Pharma/Regeneron/Teva - AdisInsight". adisinsight.springer.com.
  47. ↑ "Fulranumab - AdisInsight". adisinsight.springer.com.
  48. ↑ "GBR 900 - AdisInsight". adisinsight.springer.com.
  49. ↑ "GZ 389988 - AdisInsight". adisinsight.springer.com.
  50. ↑ "LEVI 04 - AdisInsight". adisinsight.springer.com.
  51. ↑ "NRD 135S E1 - AdisInsight". adisinsight.springer.com.
  52. ↑ https://www.novaremed.com/index.php/technology-pipeline
  53. ↑ "ONO 4474 - AdisInsight". adisinsight.springer.com.
  54. ↑ https://www.nexvet.com/therapies/chronic-pain/nv-01/
  55. ↑ "Tanezumab - Eli Lilly and Company/Pfizer - AdisInsight". adisinsight.springer.com.
  56. ↑ "VM 902 - AdisInsight". adisinsight.springer.com.
  57. ↑ "Acetaminophen/Naltrexone - Allodynic Therapeutics - AdisInsight". adisinsight.springer.com.
  58. ↑ "CR 4056 - AdisInsight". adisinsight.springer.com.
  59. ↑ "E 52862 - AdisInsight". adisinsight.springer.com.
  60. ↑ "Diclofenac sodium transdermal patch - Hisamitsu Pharmaceuticals - AdisInsight". adisinsight.springer.com.
  61. ↑ "KCP 506 - AdisInsight". adisinsight.springer.com.
  62. ↑ Moreno, Ana M.; Alemán, Fernando; Catroli, Glaucilene F.; Hunt, Matthew; Hu, Michael; et al. (10 March 2021). "Long-lasting analgesia via targeted in situ repression of NaV1.7 in mice". Science Translational Medicine . 13 (584). doi:10.1126/scitranslmed.aay9056. eISSN   1946-6242. ISSN   1946-6234. PMC   8830379 . PMID   33692134.
  63. ↑ "PAX 01 - AdisInsight". adisinsight.springer.com.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.