The role of M1 muscarinic receptor agonism of N-desmethylclozapine in the unique clinical effects of clozapine
The muscarinic receptor agonist activities of NDMC are unique among antipsychotics, and provide a possible molecular basis for the superior clinical effects of clozapine pharmacotherapy.
Intrinsic Efficacy of Antipsychotics at Human D2, D3, and D4 Dopamine Receptors: Identification of the Clozapine Metabolite N-Desmethylclozapine as a D2/D3 Partial Agonist
- E. Burstein, J. Ma, M. Brann
- Psychology, MedicineJournal of Pharmacology and Experimental…
- 1 December 2005
Using a cell-based functional assay, it is demonstrated that overexpression of Gαo induces constitutive activity in the human D2-like receptors (D2, D3, and D4) and it is proposed that bypassing clozapine blockade through direct administration of NDMC to patients may provide superior antipsychotic efficacy.
Low dose bexarotene treatment rescues dopamine neurons and restores behavioral function in models of Parkinson's disease.
- K. Mcfarland, T. Spalding, D. Hubbard, Jian‐Nong Ma, R. Olsson, E. Burstein
- BiologyACS Chemical Neuroscience
- 20 November 2013
It is hypothesize that low oral doses of bexarotene may provide an effective and tolerated therapy for Parkinson's disease (PD) at doses up to 100-fold lower than those effective in rodent cancer models.
AC-186, a selective nonsteroidal estrogen receptor β agonist, shows gender specific neuroprotection in a Parkinson's disease rat model.
In male rats, 17β-estradiol, which activates ERβ and ERα with equal potency, did not show the same neuroprotective benefits as AC-186, so in addition to a beneficial safety profile for use in both males and females, a selective ERβ agonist has a differentiated pharmacological profile compared to 17 β-ESTradiol in males.
Neuropeptide FF Receptors Have Opposing Modulatory Effects on Nociception
Evidence is provided for the opposing roles of NPFF receptors and selective FF2 agonism and/or selective FF1 antagonism are highlighted as potential targets warranting further investigation.
Characterization of Highly Efficacious Allosteric Agonists of the Human Calcium-Sensing Receptor
- Jian‐Nong Ma, Michelle L. Owens, E. Burstein
- Biology, ChemistryJournal of Pharmacology and Experimental…
- 1 April 2011
These highly efficacious CaSR allosteric agonists represent leads for developing therapeutic agents with potential advantages over existing therapies and compared their pharmacology to phenylalkylamine calcimimetics.
Creatin(in)e and Maillard reaction products as precursors of mutagenic compounds: Effects of various amino acids
Behavioral Analysis of Dopaminergic Activation in Zebrafish and Rats Reveals Similar Phenotypes.
A detailed phenotype evaluation of zebrafish larvae, measuring 300-3000 variables and analyzing them using multivariate analysis to identify the most important ones for further evaluations, corroborated findings in a parallel rat study and previous observations in humans.
Nonsteroidal selective androgen receptor modulators and selective estrogen receptor β agonists moderate cognitive deficits and amyloid-β levels in a mouse model of Alzheimer's disease.
- S. George, G. Petit, G. Gouras, P. Brundin, R. Olsson
- Biology, PsychologyACS Chemical Neuroscience
- 18 December 2013
It is found that ACP-105 given alone decreases anxiety-like behavior and when ACp-105 is administered in combination with AC-186, they increase the amyloid-β degrading enzymes neprilysin and insulin-degrading enzyme and decrease amyloids-β levels in the brain as well as improve cognition.
Discovery of a potent, orally available, and isoform-selective retinoic acid beta2 receptor agonist.
Being an isoform-selective RARbeta2 receptor agonist that discriminates between nuclear receptor isoforms having identical ligand binding domains, 2 will be useful as a pharmacological research tool but also a valuable starting point for drug development.