ArticleThe Journal of pharmacology and experimental therapeutics2014
Relationship between cerebral sigma-1 receptor occupancy and attenuation of cocaine's motor stimulatory effects in mice by PD144418.
Article in The Journal of pharmacology and experimental therapeutics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Sigma Receptor Ligands Are Potent Antiprion Compounds that Act Independently of Sigma Receptor Binding.ACS chemical neuroscience · 2024Article
- Repurposing Sigma-1 Receptor Ligands for COVID-19 Therapy?Frontiers in pharmacology · 2020Review
- Sigma-1 receptor ligand PD144418 and sigma-2 receptor ligand YUN-252 attenuate the stimulant effects of methamphetamine in mice.Psychopharmacology · 2019Article
- Cocaine-induced endocannabinoid signaling mediated by sigma-1 receptors and extracellular vesicle secretion.eLife · 2019Article
- Acute Cocaine Enhances Dopamine DMolecular neurobiology · 2019Article
- The sigma-1 receptor as a regulator of dopamine neurotransmission: A potential therapeutic target for methamphetamine addiction.Pharmacology & therapeutics · 2018Review
- Behavioral Effects of a Potential Novel TAAR1 Antagonist.Frontiers in pharmacology · 2018Article
- The sigma-1 receptor modulates methamphetamine dysregulation of dopamine neurotransmission.Nature communications · 2017Article
- Identification of the gene that codes for the σProceedings of the National Academy of Sciences of the United States of America · 2017Article
- Tactics for preclinical validation of receptor-binding radiotracers.Nuclear medicine and biology · 2017Review
- Sigma receptors [σRs]: biology in normal and diseased states.Journal of receptor and signal transduction research · 2016Article
- Crystal structure of the human σ1 receptor.Nature · 2016Article
- Cocaine occupancy of sigma1 receptors and dopamine transporters in mice.Synapse (New York, N.Y.) · 2016Article
- Characterization of pulmonary sigma receptors by radioligand binding.European journal of pharmacology · 2015Article
- Cutamesine Overcomes REM Sleep Deprivation-Induced Memory Loss: Relationship to Sigma-1 Receptor Occupancy.Molecular imaging and biology · 2015Article
- Ether modifications to 1-[2-(3,4-dimethoxyphenyl)ethyl]-4-(3-phenylpropyl)piperazine (SA4503): effects on binding affinity and selectivity for sigma receptors and monoamine transporters.Bioorganic & medicinal chemistry · 2015Article
- N-phenylpropyl-N'-substituted piperazines occupy sigma receptors and alter methamphetamine-induced hyperactivity in mice.Pharmacology, biochemistry, and behaviorArticle
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7 authors.
Funding
Abstract
Psychostimulant effects of cocaine are mediated partly by agonist actions at sigma-1 (σ1) receptors. Selective σ1 receptor antagonists attenuate these effects and provide a potential avenue for pharmacotherapy. However, the selective and high affinity σ1 antagonist PD144418 (1,2,3,6-tetrahydro-5-[3-(4-methylphenyl)-5-isoxazolyl]-1-propylpyridine) has been reported not to inhibit cocaine-induced hyperactivity. To address this apparent paradox, we evaluated aspects of PD144418 binding in vitro, investigated σ1 receptor and dopamine transporter (DAT) occupancy in vivo, and re-examined effects on locomotor activity. PD144418 displayed high affinity for σ1 sites (Ki 0.46 nM) and 3596-fold selectivity over σ2 sites (Ki 1654 nM) in guinea pig brain membranes. No appreciable affinity was noted for serotonin and norepinephrine transporters (Ki >100 μM), and the DAT interaction was weak (Ki 9.0 μM). In vivo, PD144418 bound to central and peripheral σ1 sites in mouse, with an ED50 of 0.22 μmol/kg in whole brain. No DAT occupancy by PD144418 (10.0 μmol/kg) or possible metabolites were observed. At doses that did not affect basal locomotor activity, PD144418 (1, 3.16, and 10 μmol/kg) attenuated cocaine-induced hyperactivity in a dose-dependent manner in mice. There was good correlation (r(2) = 0.88) of hyperactivity reduction with increasing cerebral σ1 receptor occupancy. The behavioral ED50 of 0.79 μmol/kg corresponded to 80% occupancy. Significant σ1 receptor occupancy and the ability to mitigate cocaine's motor stimulatory effects were observed for 16 hours after a single 10.0 μmol/kg dose of PD144418.
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