The in vitro pharmacological profile of TD-1211, a neutral opioid receptor antagonist
@article{Tsuruda2013TheIV, title={The in vitro pharmacological profile of TD-1211, a neutral opioid receptor antagonist}, author={Pamela R. Tsuruda and Ross G. Vickery and Daniel D. Long and Scott R. Armstrong and David T. Beattie}, journal={Naunyn-Schmiedeberg's Archives of Pharmacology}, year={2013}, volume={386}, pages={479-491} }
The clinical efficacy of opioid receptor antagonists for the treatment of opioid-induced constipation (OIC) is established. Peripherally selective antagonists are intended to provide OIC symptom relief without compromising the analgesic effects of centrally penetrant opioid agonists. We describe the in vitro profile of a novel opioid receptor antagonist, TD-1211, at recombinant (human μ and δ, and guinea pig κ) and rodent native opioid receptors. TD-1211 bound with high affinity to human…
11 Citations
Discovery of Axelopran (TD-1211): A Peripherally Restricted μ-Opioid Receptor Antagonist.
- BiologyACS medicinal chemistry letters
- 2019
The application of Theravance's multivalent approach to drug discovery coupled with a physicochemical property design strategy by which the N-substituted-endo-3-(8-aza-bicyclo[3.2.1]oct-3-yl)-phenyl carboxamide series of μ-opioid receptor antagonists was optimized to afford axelopran (TD-1211) 19i as a potential treatment for opioid-induced constipation is described.
The in vivo pharmacodynamics of the novel opioid receptor antagonist, TD-1211, in models of opioid-induced gastrointestinal and CNS activity
- Biology, MedicineNaunyn-Schmiedeberg's Archives of Pharmacology
- 2013
The data from these studies support the clinical development of TD-1211 as a novel treatment for opioid-induced GI dysfunction and in vivo GI activity, consistent with opioid receptor antagonism, but has no significant CNS activity.
Peripherally Acting μ-Opioid Receptor Antagonists for the Treatment of Opioid-Related Side Effects: Mechanism of Action and Clinical Implications
- Biology, MedicineJournal of pharmacy practice
- 2017
Although questions of cost-effectiveness and relative efficacy versus laxatives remain, PAMORAs can mitigate OIC and improve patient QOL and may also have applications beyond OIC, including reducing the increased cardiac risk or potential tumorigenic effects of opioids.
Discovery of N-substituted-endo-3-(8-aza-bicyclo[3.2.1]oct-3-yl)-phenol and -phenyl carboxamide series of μ-opioid receptor antagonists.
- Biology, ChemistryBioorganic & medicinal chemistry letters
- 2017
Novel Oral Therapies for Opioid‐induced Bowel Dysfunction in Patients with Chronic Noncancer Pain
- MedicinePharmacotherapy
- 2016
Investigations comparing these agents to regimens using standard laxative and combination therapy and trials in special populations and patients with active cancer are needed to further define their role in therapy.
New Options in Constipation Management
- MedicineCurrent Oncology Reports
- 2015
Evidence-based benefits of multiple new anti-constipating medications are discussed and an approach to managing constipation is outlined.
Novel therapeutic agents in neurogastroenterology: advances in the past year
- Medicine, BiologyNeurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society
- 2014
There have been significant advances in understanding the pathophysiological mechanisms in patients with neurogastroenterological disorders including irritable bowel syndrome (IBS) and functional…
An Evidence-Based Review of Novel and Emerging Therapies for Constipation in Patients Taking Opioid Analgesics
- Biology, Medicine
- 2014
An Evidence-Based Review of Novel and Emerging Therapies for Constipation in Patients Taking Opioid Analgesics concludes that these therapies have the potential to improve the quality of life in patients taking opioids.
Gastrointestinal dysmotility disorders in critically ill dogs and cats.
- MedicineJournal of veterinary emergency and critical care
- 2016
No consensus exists regarding optimal timing of initiating prophylaxic measures, preference of treatment, or duration of therapy for critically ill dogs and cats, and the prognosis for affected small animal patients remains unknown.
References
SHOWING 1-10 OF 71 REFERENCES
The in vitro pharmacological profile of TD-5108, a selective 5-HT4 receptor agonist with high intrinsic activity
- Biology, MedicineNaunyn-Schmiedeberg's Archives of Pharmacology
- 2008
The high intrinsic activity and preferential binding of TD-5108 to 5- HT4 over other 5-HT receptors may result in an improved clinical profile for the treatment of gastrointestinal disorders of reduced motility.
The in vitro pharmacology of the peripherally restricted opioid receptor antagonists, alvimopan, ADL 08-0011 and methylnaltrexone
- Biology, MedicineNaunyn-Schmiedeberg's Archives of Pharmacology
- 2007
It is concluded that alvimopan, ADL 08-0011, and methylnaltrexone differ in their in vitro pharmacological properties, particularly with respect to opioid receptor subtype selectivity and intrinsic activity.
The in vivo pharmacodynamics of the novel opioid receptor antagonist, TD-1211, in models of opioid-induced gastrointestinal and CNS activity
- Biology, MedicineNaunyn-Schmiedeberg's Archives of Pharmacology
- 2013
The data from these studies support the clinical development of TD-1211 as a novel treatment for opioid-induced GI dysfunction and in vivo GI activity, consistent with opioid receptor antagonism, but has no significant CNS activity.
Different Effects of Opioid Antagonists on μ-, δ-, and κ-Opioid Receptors with and without Agonist Pretreatment
- Biology, PsychologyJournal of Pharmacology and Experimental Therapeutics
- 2007
It is demonstrated that antagonist efficacy is context-dependent, possibly accounting for paradoxical pharmacological effects, and activity profiles at the three opioid receptors under different conditions could lead to antagonists with optimal clinical properties in treatment of addiction and adverse opioid effects.
[3H]Alvimopan binding to the μ opioid receptor: Comparative binding kinetics of opioid antagonists
- Biology, Medicine
- 2005
Basal opioid receptor activity, neutral antagonists, and therapeutic opportunities.
- BiologyLife sciences
- 2005
[(3)H]Alvimopan binding to the micro opioid receptor: comparative binding kinetics of opioid antagonists.
- Biology, MedicineEuropean journal of pharmacology
- 2005
Consistent with its long duration of action, alvimopan has a slow dissociation rate from the micro opioid receptor compared to other shorter acting antagonists and may be more potent if administered prior to dosing with exogenous opioids.
The opioid receptors in the hamster vas deferens are of the δ-type
- Biology, MedicineNeuropharmacology
- 1985
The opioid receptors in the hamster vas deferens are of the delta-type.
- Biology, MedicineNeuropharmacology
- 1985
The motor responses of the isolated vas deferens of the hamster were unaffected by opioid-receptor agonists, while agonists which show degrees of selectivity for the delta-opioid receptor caused dose-related inhibition of the stimulation-evoked contractions.
Peripherally Acting Mu-Opioid Receptor Antagonists and Postoperative Ileus: Mechanisms of Action and Clinical Applicability
- MedicineAnesthesia and analgesia
- 2009
The mechanisms by which POI occurs and the role of opioids and opioid receptors in the enteric nervous system are summarized, the mechanism of action of PAM-OR antagonists is discussed, and clinical pharmacology and Phase II/III POI trial results of methylnaltrexone and alvimopan are reviewed.