AMPA receptor antagonists(Glutamate receptor ionotropic AMPA antagonists), GluR-5 antagonists(Glutamate receptor 5 antagonists), Kainate receptor antagonists

Therapeutic Areas

Nervous System Diseases

Active Indication

Pain

Inactive Indication

Diabetic peripheral neuropathic painHyperalgesiaOsteoarthritis, Knee

Originator Organization

Eli Lilly & Co.

Active Organization

Lilly SA

Inactive Organization

Eli Lilly & Co.

TorreyPines Therapeutics, Inc.

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Structure

Molecular FormulaC17H20ClN5O3

InChIKeyLAKQPSQCICNZII-NOHGZBONSA-N

CAS Registry503294-13-1

Clinical Trials associated with Dasolampanel

NCT00785577 / CompletedPhase 2

A Phase 2 Study of the Effects of LY545694, an iGluR5 Antagonist, in the Treatment of Subjects With Painful Diabetic Neuropathy.

The purpose of this study is to test whether a new treatment will be safe and effective in treating pain. Patients with diabetic peripheral neuropathy will be included.

Start Date01 Nov 2008

Sponsor / Collaborator

Eli Lilly & Co.

NCT00790790 / CompletedPhase 2

A Phase 2 Study of the Effects of LY545694, an iGluR5 Antagonist, in the Treatment of Subjects With Osteoarthritis Knee Pain

To gather data on whether a new drug for osteoarthritis knee pain will be safe and have an effect on pain levels.

Start Date01 Nov 2008

Sponsor / Collaborator

Eli Lilly & Co.

NCT00832546 / CompletedPhase 1

A Double-Blind, Randomized, Placebo Controlled, Cross-Over, Safety Tolerance and Experimental Hyperalgesia Study of Oral NGX426 in Healthy Male Volunteers

The purpose of this study is to determine the effects of NGX426 on intradermal capsaicin induced pain in hyperalgesia.

Start Date01 May 2008

Sponsor / Collaborator

TorreyPines Therapeutics, Inc.

100 Clinical Results associated with Dasolampanel

100 Translational Medicine associated with Dasolampanel

100 Patents (Medical) associated with Dasolampanel

Literatures (Medical) associated with Dasolampanel

01 Nov 2016·The AAPS JournalQ3 · MEDICINE

Physiologically Based Absorption Modeling to Design Extended-Release Clinical Products for an Ester Prodrug

Q3 · MEDICINE

Article

Author: Ding, Xuan ; Day, Jeffrey S ; Sperry, David C

Absorption modeling has demonstrated its great value in modern drug product development due to its utility in understanding and predicting in vivo performance. In this case, we integrated physiologically based modeling in the development processes to effectively design extended-release (ER) clinical products for an ester prodrug LY545694. By simulating the trial results of immediate-release products, we delineated complex pharmacokinetics due to prodrug conversion and established an absorption model to describe the clinical observations. This model suggested the prodrug has optimal biopharmaceutical properties to warrant developing an ER product. Subsequently, we incorporated release profiles of prototype ER tablets into the absorption model to simulate the in vivo performance of these products observed in an exploratory trial. The models suggested that the absorption of these ER tablets was lower than the IR products because the extended release from the formulations prevented the drug from taking advantage of the optimal absorption window. Using these models, we formed a strategy to optimize the ER product to minimize the impact of the absorption window limitation. Accurate prediction of the performance of these optimized products by modeling was confirmed in a third clinical trial.

01 Jun 2014·PainQ1 · MEDICINE

Results from clinical trials of a selective ionotropic glutamate receptor 5 (iGluR5) antagonist, LY5454694 tosylate, in 2 chronic pain conditions

Q1 · MEDICINE

Article

Author: William R. Prucka ; Smriti Iyengar ; Amy S. Chappell ; Evelyn D. Lobo

This article reports results of 2 studies investigating LY545694 in pain due to osteoarthritis (OA) of the knee and diabetic peripheral neuropathic pain (DPNP). Study I randomized patients to either of 2 doses of LY545694 or to placebo, and study II randomized patients to either of 3 doses of LY545694, to pregabalin, or to placebo. No significant differences between LY545694 groups and placebo were observed on the primary (average pain severity) or secondary efficacy measures in either study. Notably, study I lacked an active control, and, in study II, pregabalin, did not separate from placebo. Treatment-emergent nausea, vomiting, and dizziness were significantly more frequent in the LY545694 groups in both trials (P⩽.05), and significantly more LY545694-treated patients discontinued because of adverse events (P<.001). Steady-state concentrations of LY545694 were comparable in patients in both studies but were lower than exposures required for efficacy in animal models of pain behavior. Because the active control did not separate from placebo in the DPNP study, the study was potentially failed, rather than negative. Without an active control, it is unknown whether the OA study was negative or failed. Consequently, efficacy of selective ionotropic glutamate receptor antagonism in chronic pain conditions may warrant further investigation. Future trials should consider different pain conditions, contain a positive control with larger patient numbers per arm, and be conducted within a single region.

01 May 2014·PainQ1 · MEDICINE

Safety, tolerability, pharmacokinetics, and effects on human experimental pain of the selective ionotropic glutamate receptor 5 (iGluR5) antagonist LY545694 in healthy volunteers

Q1 · MEDICINE

Article

Author: Karin L. Petersen ; Smriti Iyengar ; Evelyn D. Lobo ; Haatem Reda ; Amy S. Chappell ; Steven J. Verfaille ; William R. Prucka

The objective of this study was to establish in healthy volunteers the maximally tolerated multiple dose (MTMD) of the ionotropic glutamate receptor 5 antagonist LY545694 (part A), and to investigate whether that dose had analgesic or antihyperalgesic effects in the brief thermal stimulation (BTS) pain model (Part B). Part A was a double-blind, placebo-controlled study in 3 groups of 10 healthy men. To simulate an extended-release formulation, study drug was administered orally over 6hours (12 equally divided aliquots at 30-minute intervals). Part B was a double-blind, placebo-controlled, double-dummy, 3-way crossover study in 27 healthy men. At each of the 3 study periods, subjects received either LY545694 (MTMD; as determined during part A) as a simulated, twice daily extended-release formulation for 4 doses over 3days, gabapentin (600mg 8hours apart; 6 doses over 3days; positive control), or matching placebo. The BTS model was induced twice with a 1-hour interval on each of the 2 study days, before drug administration and at the time of expected peak analgesia of LY545694. Plasma exposure for LY545694 was approximately linear over the 25- to 75-mg dose range. The MTMD of LY545694 was 25mg twice daily. Areas of secondary hyperalgesia were significantly smaller after administration of LY545694 and gabapentin compared with placebo (P<.0001 and P=.0004, respectively), but there was no difference between areas after administration of gabapentin and LY545694 (P=.400). Neither gabapentin nor LY545694 reduced the painfulness of skin heating during BTS model induction. The most common treatment-emergent adverse event was dizziness. The results of this study suggest that LY545694 should be explored further as a potential treatment for chronic pain involving neuronal sensitization.

News (Medical) associated with Dasolampanel

04 Jun 2008

·www.biospace.com

TorreyPines Therapeutics, Inc. Initiates Clinical Trial to Evaluate Analgesic Effect of Oral Prodrug of Tezampanel

LA JOLLA, Calif., June 4 /PRNewswire-FirstCall/ -- TorreyPines Therapeutics, Inc. today announced it has initiated a clinical trial to evaluate the analgesic effect of NGX426, the oral prodrug of its lead product candidate, tezampanel. The randomized, double-blind, placebo-controlled Phase I trial will enroll 18 healthy volunteers at a single center in the United States. The trial is designed to evaluate the compound's safety and tolerability and to assess the time of onset, magnitude and duration of its analgesic effect. Specifically, the study will evaluate the effect of NGX426 on hyperalgesia, an abnormally increased pain state, and allodynia, pain resulting from normally non-painful stimuli to the skin, induced by intradermal injections of capsaicin. The primary endpoint is subject self-report of spontaneous pain following the injection of capsaicin. "We believe there is a substantial commercial opportunity for NGX426 as a novel, oral analgesic," said Neil Kurtz, M.D., President and Chief Executive Officer of TorreyPines Therapeutics. "Data we have obtained in our ongoing Phase I maximum tolerated dose study demonstrate that the drug is well-tolerated at single doses up to and including 210 mg and that NGX426 is rapidly converted to tezampanel. Moreover, this capsaicin study, if successful, will enable us to further take advantage of the versatility of NGX426 and the overall tezampanel franchise." Subjects in the trial, which involves the recognized and validated capsaicin-induced pain model, will receive single doses of 90 mg and 150 mg of NGX426 versus placebo in a three-way crossover design. Tezampanel is the first AMPA/kainate-type glutamate receptor antagonist to be studied in clinical trials for chronic pain. Glutamate receptors mediate the functioning of glutamate, an important excitatory neurotransmitter. While normal glutamate production is essential, excess glutamate production, either through injury or disease, can have a range of pathological effects. By acting at both the AMPA and kainate receptor site to competitively block the binding of glutamate, tezampanel and its oral prodrug, NGX426, have the potential to treat a number of diseases and disorders. These include migraine and other forms of chronic pain such as neuropathic pain, muscle spasticity and rigidity, thrombosis, epilepsy, Parkinson's disease and a condition known as central sensitization, a persistent state of hypersensitivity to pain that is a core component of many pain conditions. About TorreyPines Therapeutics TorreyPines Therapeutics, Inc. is a biopharmaceutical company committed to providing patients with better alternatives to existing therapies through the research, development and commercialization of small molecule compounds. The company's goal is to develop versatile product candidates, each capable of treating a number of acute and chronic diseases and disorders such as migraine, chronic pain, muscle spasticity and rigidity, xerostomia and cognitive disorders. The company is currently developing four product candidates: two ionotropic glutamate receptor antagonists and two muscarinic receptor agonists. Further information is available at This press release contains forward-looking statements or predictions. Such forward-looking statements include, but are not limited to, statements regarding the potential for NGX426 as a novel, oral analgesic and the potential for tezampanel and NGX426 as treatments for migraine and other forms of chronic pain such as neuropathic pain, muscle spasticity and rigidity, thrombosis, epilepsy, Parkinson's disease and central sensitization. Such statements are subject to numerous known and unknown risks, uncertainties and other factors, which may cause TorreyPines' actual results to be materially different from historical results or from any results expressed or implied by such forward-looking statements, including whether any preclinical studies or clinical trials conducted in the future, will prove successful, and if successful, whether the results can be replicated. These and other risks which may cause results to differ are described in greater detail in the "Risk Factors" section of TorreyPines' annual report on Form 10-K for the year ended December 31, 2007 and TorreyPines other SEC reports. The forward-looking statements are based on current information that is likely to change and speak only as of the date hereof. CONTACT: Company, Paul Schneider of TorreyPines Therapeutics, Inc., +1-858-623-5665, ext. 125, pschneider@torreypinestherapeutics.com; or Media, David Schull of Russo Partners, LLC, +1-212-845-4271, david.schull@russopartnersllc.com; or Investors, Rhonda Chiger of Rx Communications, +1-917-322-2569, rchiger@rxir.com, both for TorreyPines Therapeutics, Inc.

Small molecular drug

100 Deals associated with Dasolampanel

External Link

KEGG	Wiki	ATC	Drug Bank
D10107	Dasolampanel	-	-

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Diabetic peripheral neuropathic pain	Phase 2	US	Eli Lilly & Co.	01 Nov 2008
Diabetic peripheral neuropathic pain	Phase 2	PR	Eli Lilly & Co.	01 Nov 2008
Diabetic peripheral neuropathic pain	Phase 2	MX	Eli Lilly & Co.	01 Nov 2008
Osteoarthritis, Knee	Phase 2	PR	Eli Lilly & Co.	01 Nov 2008
Osteoarthritis, Knee	Phase 2	US	Eli Lilly & Co.	01 Nov 2008
Osteoarthritis, Knee	Phase 2	RO	Eli Lilly & Co.	01 Nov 2008
Pain	Preclinical	ES	Lilly SA	01 Dec 2013
Hyperalgesia	Discovery	US	TorreyPines Therapeutics, Inc.	01 May 2008

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00790790 (CTgov)	Phase 2	Osteoarthritis, Knee	147	Placebo (Placebo)	mfxwjlhowz(yutbtfhnif) = zqvmwktfhy cpgaoobmgt (lymvecawam, muvxkjxxhf - tejqiqxuxq) View more	-	05 Oct 2011
				LY545694 49 mg (LY545694 49 mg)	mfxwjlhowz(yutbtfhnif) = briucpwdnf cpgaoobmgt (lymvecawam, fddetydvfs - vwfzjntndr) View more

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