Safety, Tolerability, and Pharmacokinetics of Mevidalen (LY3154207), a Centrally Acting Dopamine D1 Receptor‐Positive Allosteric Modulator (D1PAM), in Healthy Subjects
Sign Up to like & getrecommendations! Published in 2020 at "Clinical Pharmacology in Drug Development"
DOI: 10.1002/cpdd.874
Abstract: Activation of the brain dopamine D1 receptor has attracted attention because of its promising role in neuropsychiatric diseases. Although efforts to develop D1 agonists have been challenging, a positive allosteric modulator (PAM), represents an attractive… read more here.
Keywords: allosteric modulator; mevidalen ly3154207; healthy subjects; dopamine receptor ... See more keywords
Safety, Tolerability, and Pharmacokinetics of Multiple Repeated Oral Doses of the α2/3/5‐Subtype Selective GABAA‐Positive Allosteric Modulator PF‐06372865 in Healthy Volunteers
Sign Up to like & getrecommendations! Published in 2021 at "Clinical Pharmacology in Drug Development"
DOI: 10.1002/cpdd.912
Abstract: Multiple‐dose pharmacokinetics (PK) and safety were investigated in this phase 1 study of PF‐06372865, a positive allosteric modulator of α2/3/5 subunit‐containing γ‐aminobutyric acid A receptors (NCT03351751). In 2 cohorts (7‐8 PF‐06372865 and 2 placebo in… read more here.
Keywords: allosteric modulator; oral doses; safety; twice daily ... See more keywords
Muscarinic-3-receptor positive allosteric modulator ASP8302 in patients with underactive bladder. A randomized controlled trial.
Sign Up to like & getrecommendations! Published in 2022 at "Neurourology and urodynamics"
DOI: 10.1002/nau.24931
Abstract: AIM The aim of this study is to evaluate safety and efficacy of ASP8302, a novel positive allosteric modulator for the muscarinic M3 receptor (M3-PAM), in patients with underactive bladder (UAB). METHODS A randomized, double-blind,… read more here.
Keywords: muscarinic receptor; allosteric modulator; placebo; bladder ... See more keywords
Co-modulation of an allosteric modulator of nicotinic receptor-cholinesterase inhibitor (galantamine) and a 5-HT4 receptor agonist (RS-67333): effect on scopolamine-induced memory deficit in the mouse
Sign Up to like & getrecommendations! Published in 2017 at "Psychopharmacology"
DOI: 10.1007/s00213-017-4664-z
Abstract: AimIt is widely assumed that the upcoming therapeutics for Alzheimer’s disease will require to act on more than one target to be effective. We investigated here whether a combination of the nicotinic receptor allosteric modulator/cholinesterase… read more here.
Keywords: allosteric modulator; nicotinic receptor; galantamine; effect ... See more keywords
The structural determinants of the bitopic binding mode of a negative allosteric modulator of the dopamine D2 receptor
Sign Up to like & getrecommendations! Published in 2018 at "Biochemical Pharmacology"
DOI: 10.1016/j.bcp.2018.01.002
Abstract: Graphical abstract Figure. No caption available. ABSTRACT SB269652 is a negative allosteric modulator of the dopamine D2 receptor (D2R) yet possesses structural similarity to ligands with a competitive mode of interaction. In this study, we… read more here.
Keywords: allosteric modulator; negative allosteric; dopamine receptor; pharmacology ... See more keywords
Distinctive binding properties of the negative allosteric modulator, [3H]SB269,652, at recombinant dopamine D3 receptors
Sign Up to like & getrecommendations! Published in 2018 at "European Journal of Pharmacology"
DOI: 10.1016/j.ejphar.2017.12.002
Abstract: ABSTRACT Recently, employing radioligand displacement and functional coupling studies, we demonstrated that SB269,652 (N‐[(1r,4r)−4‐[2‐(7‐cyano‐1,2,3,4‐tetrahydroisoquinolin‐2‐yl)ethyl]cyclohexyl]−1H‐indole‐2‐carboxamide) interacts in an atypical manner with dopamine D3 receptor displaying a unique profile reminiscent of a negative allosteric ligand. Here, we… read more here.
Keywords: allosteric modulator; negative allosteric; dopamine; sb269 652 ... See more keywords
Agathadiol, a labdane diterpenoid from juniper berries, is a positive allosteric modulator of CB1R.
Sign Up to like & getrecommendations! Published in 2021 at "Fitoterapia"
DOI: 10.1016/j.fitote.2021.105059
Abstract: The neutral fraction of a juniper (Juniperus communis L.) berries acetone extract could positively modulate the activity of type 1 - cannabinoid receptor (CB1R). Bioactivity-directed fractionation identified the labdane diterpenoid agathadiol (4) as a positive… read more here.
Keywords: allosteric modulator; cb1r; juniper; labdane diterpenoid ... See more keywords
Synthesis of an allosteric modulator of ionotropic glutamate receptors
Sign Up to like & getrecommendations! Published in 2020 at "Mendeleev Communications"
DOI: 10.1016/j.mencom.2020.03.008
Abstract: Synthesis of 6-[4-methoxy-3-(pyrrolidin-1-ylmethyl)benzyl]-1,11-dimethyl-3,6,9-triazatricyclo[7.3.1.13,11]tetradecane-4,8,12-trione has been carried out and optimized. In vitro studies using electrophysiological patch clamp technique have revealed a negative effect of this compound on kainateinduced currents in Purkinje neurons in a wide range… read more here.
Keywords: allosteric modulator; modulator ionotropic; glutamate receptors; ionotropic glutamate ... See more keywords
Discovery of an Orally Efficacious Positive Allosteric Modulator of the Glucagon-like Peptide-1 Receptor.
Sign Up to like & getrecommendations! Published in 2021 at "Journal of medicinal chemistry"
DOI: 10.1021/acs.jmedchem.1c00029
Abstract: The identification of LSN3318839, a positive allosteric modulator of the glucagon-like peptide-1 receptor (GLP-1R), is described. LSN3318839 increases the potency and efficacy of the weak metabolite GLP-1(9-36)NH2 to become a full agonist at the GLP-1R… read more here.
Keywords: allosteric modulator; glucagon like; glp; modulator glucagon ... See more keywords
Discovery of a Biased Allosteric Modulator for Cannabinoid 1 Receptor: Preclinical Anti-Glaucoma Efficacy.
Sign Up to like & getrecommendations! Published in 2021 at "Journal of medicinal chemistry"
DOI: 10.1021/acs.jmedchem.1c00040
Abstract: We apply the magic methyl effect to improve the potency/efficacy of GAT211, the prototypic 2-phenylindole-based cannabinoid type-1 receptor (CB1R) agonist-positive allosteric modulator (ago-PAM). Introducing a methyl group at the α-position of nitro group generated two… read more here.
Keywords: allosteric modulator; cb1r allosteric; efficacy; glaucoma ... See more keywords
Synthesis and Preclinical Characterization of LY3154885, a Human Dopamine D1 Receptor Positive Allosteric Modulator with an Improved Nonclinical Drug-Drug Interaction Risk Profile.
Sign Up to like & getrecommendations! Published in 2022 at "Journal of medicinal chemistry"
DOI: 10.1021/acs.jmedchem.1c01887
Abstract: Results from recently completed clinical studies suggest the dopamine D1 receptor positive allosteric modulator (PAM) mevidalen (1) could offer unique value for lewy body dementia (LBD) patients. In nonclinical assessments, 1 was mainly eliminated by… read more here.
Keywords: allosteric modulator; dopamine receptor; receptor positive; risk ... See more keywords