A5027256754- Neurotransmitter Receptor Influence on Behavior
- Neuroscience and Neuropharmacology Research
- Receptor Mechanisms and Signaling
- Neurological disorders and treatments
- Cyclopropane Reaction Mechanisms
- Parkinson's Disease Mechanisms and Treatments
- Catalytic Cross-Coupling Reactions
- Genetic Neurodegenerative Diseases
- Synthesis and Biological Evaluation
- Medical Imaging Techniques and Applications
- Chemical synthesis and alkaloids
- Computational Drug Discovery Methods
- Catalytic C–H Functionalization Methods
- Synthesis and Reactivity of Heterocycles
- Autism Spectrum Disorder Research
- Oxidative Organic Chemistry Reactions
- Attention Deficit Hyperactivity Disorder
- Asymmetric Synthesis and Catalysis
- Coordination Chemistry and Organometallics
- Phosphodiesterase function and regulation
- Synthesis and pharmacology of benzodiazepine derivatives
- Synthesis of Organic Compounds
- Chemical Synthesis and Analysis
- Neurology and Historical Studies
- Neuropeptides and Animal Physiology
Integrative Research Laboratories
2016-2025
University of Gothenburg
1993-2020
University of Cagliari
2020
Karolinska Institutet
2020
University of Bradford
2020
Manchester Academic Health Science Centre
2020
University of Manchester
2020
Columbia University
2013
United States Congress
2013
Universidade Federal de Minas Gerais
2013
Abstract Background The treatment of levodopa‐induced dyskinesia in Parkinson's disease (PD) is a largely unmet need. Objectives Mesdopetam novel small molecule dopamine D3 receptor antagonist aimed for the dyskinesia. This was phase 2b study dose finding to investigate efficacy and safety 2.5 mg, 5 mg 7,5 b.i.d. randomized controlled trial. Methods PD patients with ≥2 hours troublesome were placebo or mesdopetam twice daily 12 weeks. primary endpoint change from baseline week ON time...
A series of (S)-phenylpiperidines in which the substituents on aromatic ring and nitrogen have been varied has prepared. They evaluated pharmacologically to explore importance these for interaction with central dopamine (DA) receptors. On basis biochemical behavioral data rats, several compounds are characterized as centrally acting DA autoreceptor antagonists. (S)-Phenylpiperidines having an substituent a high group dipole moment 3-position, i.e., meta respect piperidine ring, being...
Objectives: To evaluate the efficacy and safety of dopaminergic stabilizer pridopidine (ACR16) in patients with Huntington's disease (HD). Methods: In a randomized, double-blind, placebo-controlled, 4-week trial, HD received (50 mg/d, n = 28) or placebo (n 30). The primary outcome measure was change from baseline weighted cognitive score, assessed by tests (Symbol Digit Modalities, verbal fluency, Stroop tests). Secondary measures included changes Unified Disease Rating Scale, Hospital...
Pridopidine (ACR16) belongs to a new pharmacological class of agents affecting the central nervous system called dopaminergic stabilizers. Dopaminergic stabilizers act primarily at dopamine type 2 (D(2)) receptors and display state-dependent behavioural effects. This article aims give an overview preclinical neurochemical in vivo properties pridopidine. was given s.c. male Sprague-Dawley rats (locomotor, microdialysis tissue neurochemistry) i.p. Swiss mice (tail suspension test)....
Modification of the partial dopamine type 2 receptor (D(2)) agonist 3-(1-benzylpiperidin-4-yl)phenol (9a) generated a series novel functional D(2) antagonists with fast-off kinetic properties. A representative this series, pridopidine (4-[3-(methylsulfonyl)phenyl]-1-propylpiperidine; ACR16, 12b), bound competitively low affinity to in vitro, without displaying properties essential for interaction inactive state, thereby allowing receptors rapidly regain responsiveness. In vivo, neurochemical...
Arylation of 1-(methoxycarbonyl)-2,5-dihydropyrrole under standard Heck reaction conditions produces a mixture compounds. The olefin undergoes two types palladium-catalyzed reactions: (a) arylation to provide C-3 arylated derivatives and (b) competing double bond isomerization. Addition silver carbonate thallium acetate fully suppressed the isomerization, good yields substituted compounds were achieved after with aryl halides. With regard triflates as arylating agents, addition lithium...
(-)-OSU6162 is a substituted (S)-3-phenylpiperidine derivative which exhibits some affinity to the dopamine D2 receptor family. In vivo, compound displays unique normalizing profile on psychomotor activity by an intriguing mixture of stimulatory and inhibitory properties. present investigation, effects central dopaminergic function were studied positron emission tomography (PET) L-[11C]DOPA in anaesthetized female rhesus monkeys. displayed tone-dependent effect with reduction striatal influx...
IRL790 ([2-(3-fluoro-5-methanesulfonylphenoxy)ethyl](propyl)amine, mesdopetam) is a novel compound in development for the clinical management of motor and psychiatric disabilities Parkinson disease. The discovery was made applying systems pharmacology approach based on vivo response profiling. chemical design idea to develop new type DA D3/D2 receptor antagonist built agonist rather than structural motifs. We hypothesized that such dopamine with physicochemical properties similar agonists...
Huntington’s disease (HD) is a hereditary, incurable neurodegenerative disorder characterized by progressive loss of frontostriatal integrity.1 Clinically, movement disorder, dementia, and liability for behavioral disturbances psychosis characterize the disorder. It well known that dopaminergic drugs modify some clinical features HD. In this respect, different agonists antagonists function may improve or worsen chorea. Whereas levodopa offer relief from hypokinesia, concomitant worsening...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSubstituted 3-phenylpiperidines: new centrally acting dopamine autoreceptor antagonistsClas Sonesson, Nicholas Waters, Kjell Svensson, Arvid Carlsson, Martin W. Smith, Montford F. Piercey, Eddi Meier, and Haakan WikstroemCite this: J. Med. Chem. 1993, 36, 21, 3188–3196Publication Date (Print):October 1, 1993Publication History Published online1 May 2002Published inissue 1 October...
IRL790 is a novel compound with psychomotor stabilizing properties primarily targeting the dopamine D3 receptor. developed as an experimental treatment for levodopa-induced dyskinesia (LID), impulse control disorder, and psychosis in Parkinson's disease (PD). The primary objective was to investigate safety tolerability of PD patients LID randomized controlled trial. peak-dose were placebo or (1:3 ratio) 4 weeks. Study drug given adjunct patients' regular stable antiparkinsonian medication....
Abstract Background IRL752 is a novel small‐molecule compound that acts to regioselectively enhance norepinephrine, dopamine, and acetylcholine neurotransmission in the cerebral cortex. Objective The primary objective of trial was investigate safety tolerability patients with Parkinson's disease dementia. Methods Patients dementia were randomized or placebo treatment (3:1 ratio) for 28 days. study drug given as an adjunct patients’ regular stable antiparkinsonian medication. Dosing...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTOn the Quantitative Structure-Activity Relationships of Meta-Substituted (S)-Phenylpiperidines, a Class Preferential Dopamine D2 Autoreceptor Ligands: Modeling Synthesis and Release in Vivo by Means Partial Least Squares RegressionLars O. Hansson, Nicholas Waters, Susanna Holm, Clas SonessonCite this: J. Med. Chem. 1995, 38, 16, 3121–3131Publication Date (Print):August 1, 1995Publication History Published online1 May 2002Published inissue 1 August...
A series of para-substituted 4-phenylpiperidines/piperazines have been synthesized and their affinity to recombinant rat cerebral cortex monoamine oxidases (MAO A) B B) determined. Para-substituents with low dipole moment increased the MAO A, whereas groups high yielded compounds no or weak affinity. In contrast, properties affecting were polarity bulk para-substituent, large hydrophobic substituents producing addition, these tested in freely moving rats effect on post-mortem neurochemistry...
A series of 1-propyl-4-arylpiperidines were synthesized and their effects on the dopaminergic serotonergic systems tested in vivo vitro. Scaffold jumping among five- six-membered bicyclic aryl rings attached to piperidine ring had a marked impact these effects. Potent selective dopamine D(2) receptor antagonists generated from 3-indoles, 3-benzoisoxazoles, 3-benzimidazol-2-one, 3-benzothiophenes. In contrast, 3-benzofuran was potent inhibitor monoamine oxidase (MAO) A. The compounds...
This paper describes the application of in vivo systems response profiling CNS drug discovery by a process referred to as Integrative Screening Process. The biological profile, treated an array, is used major outcome for selection candidate drugs. Dose–response data, including ex brain monoaminergic biomarkers and behavioral descriptors, are systematically collected analyzed principal component analysis (PCA) partial least-squares (PLS) regression, yielding multivariate characterization...