- |||||||||| Review, Journal: Implications of the non-neuronal cholinergic system for therapeutic interventions of inflammatory skin diseases. (Pubmed Central) - Oct 18, 2024
We highlight the impact of the NNCS on prevalent skin diseases such as psoriasis, atopic dermatitis, rosacea, acne, bullous diseases, hyperhidrosis and hypohidrosis, illustrating its significance in disease pathogenesis and therapy. This comprehensive overview aims to enhance understanding of the NNCS's role in skin health and disease, offering a foundation for future research and therapeutic innovation.
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Journal: Muscarinic modulation of synaptic transmission and short-term plasticity in the dorsal and ventral hippocampus. (Pubmed Central) - Jun 13, 2024 In this study we show that the nonselective muscarinic receptor agonist carbachol similarly suppresses basal synaptic transmission in the dorsal and ventral CA1 hippocampal field, in a concentration-depended manner...Using the M2 receptor antagonist gallamine and the M4 receptor antagonist tropicamide, we found that M2 receptors are involved in controlling basal synaptic transmission and short-term synaptic plasticity (STSP) in the ventral but not the dorsal hippocampus, while M4 receptors participate in modulating basal synaptic transmission and STSP in both segments of the hippocampus...Furthermore, M4 receptors appear to exert a permissive role on the actions of M2 receptors on STSP in the ventral hippocampus. This dorsoventral differentiation of muscarinic modulation is expected to have important implications in information processing along the endogenous hippocampal circuitry.
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Clinical, Journal: Efficacy and Safety of Xanomeline-Trospium Chloride in Schizophrenia: A Randomized Clinical Trial. (Pubmed Central) - May 1, 2024 P3 These findings, together with the previously reported and consistent results from the EMERGENT-1 and EMERGENT-2 trials, support the potential of xanomeline-trospium to be the first in a putative new class of antipsychotic medications without D2 dopamine receptor blocking activity. ClinicalTrials.gov Identifier: NCT04738123.
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Response to Karxt in Short-Term Placebo-Controlled Trials in Schizophrenia (Salon 4) - Apr 29, 2024 - Abstract #ASCP2024ASCP_243; P2, P3 This result is comparable to established antipsychotics such as aripiprozole and risperdone, which have shown similar response rates in short-term placebo-controlled trials, although no head-to-head trials have been completed to date. No clinical or demographic factors measured at baseline distinguished KarXT responders from non-responders.
- |||||||||| diphenhydramine / Generic mfg., epinephrine / Generic mfg.
Bronchoprovocation Test Gone Awry (San Diego Convention Center, Area H (Hall H, Ground Level)) - Feb 20, 2024 - Abstract #ATS2024ATS_5635; Methacholine anaphylaxis is currently an unknown entity but can physiologically be explained by its broncho-constrictive properties. Although this may have been an isolated incident, it is important to create awareness that even benign medications that are commonly used can cause serious adverse events in certain populations.
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Journal: Vasodilators activate the anion channel TMEM16A in endothelial cells to reduce blood pressure. (Pubmed Central) - Nov 18, 2023 TMEM16A channels generated calcium (Ca)-activated Cl currents in endothelial cells from control (TMEM16A) mice that were absent in those from mice with tamoxifen-inducible, endothelial cell-specific knockout of TMEM16A (TMEM16A ecKO)...These data indicate that vasodilators stimulate TRPV4 channels, leading to Ca-dependent activation of nearby TMEM16A channels in endothelial cells to produce arterial hyperpolarization, vasodilation, and reduced blood pressure. Thus, TMEM16A is an anion channel in endothelial cells that regulates arterial contractility and blood pressure.
- |||||||||| pilocarpine / Generic mfg.
Journal: Transdermal iontophoretic application of l-NAME is available in sweating research induced by heat stress in young healthy adults. (Pubmed Central) - Sep 18, 2023 In protocol 1, 0.001% and 1% pilocarpine were iontophoretically administered at l-NAME-treated and untreated sites...Notably, these observations are consistent with prior sweating studies administrating l-NAME into human skin using intradermal microdialysis techniques. Based on the similarity of our results with already known observations, we conclude that transdermal iontophoresis of l-NAME is a valid non-invasive technique for the investigation of the mechanisms of sweating related to NOS during heat stress.
- |||||||||| Journal: Increased Metabolic Potential, Efficacy, and Safety of Emerging Treatments in Schizophrenia. (Pubmed Central) - Jul 20, 2023
Novel targets and preclinical and clinical data on emerging treatments, such as glycine transport inhibitors, nicotinic and muscarinic receptor agonists, and trace amine-associated receptor-1 agonists, offer promise toward relevant therapeutic advancements. Numerous areas of investigation currently exist with the potential to considerably progress our knowledge and treatment of schizophrenia.
- |||||||||| xanomeline/trospium (KarXT) / PureTech
Evaluating KarXT [xanomeline (In-Person) - Jul 6, 2023 - Abstract #AAIC2023AAIC_8152; The findings suggest that activation of M muscarinic receptors modifies glutamate transmission in the dorsolateral striatum and self-grooming behavior. The trial design of the ADEPT-1 study is an efficient way to assess the potential for KarXT to provide clinically meaningful benefit in preventing the return of ADP in patients who have responded to KarXT.
- |||||||||| Miostat (carbachol) / Novartis
Acetylcholine acts as a cell-type-specific switch for behavioral timescale activity (Montreal Bonaventure Hotel (CAN meeting headquarters)) - Jun 10, 2023 - Abstract #CANACN2023CAN_ACN_135; Upon application of carbachol (CCh), an ACh nicotinic and muscarinic receptor agonist, we also found differential responses to both chronic and transient application of CCh...In total, our results illustrate ACh reorganizes subicular activity in a cell-type-specific manner and can influence cellular dynamics on slow and behaviorally relevant timescales. As such, the subiculum may contain an ACh dependent microcircuit responsible for memory encoding.
- |||||||||| quetiapine / Generic mfg.
Quetiapine-induced Hypoglycemia in an Elderly Non-diabetic Patient with Dementia (Station 9,The Poster Experience) - Mar 25, 2023 - Abstract #AACE2023AACE_217; In addition to quetiapine, there are case reports of hypoglycemia occurring during treatment with risperidone, olanzapine, aripiprazole, and paliperidone. Clozapine and olanzapine increase insulin release from isolated pancreatic islets in vitro, though quetiapine did not demonstrate this effect...The physiologic pathway by which SGA
- |||||||||| xanomeline/trospium (KarXT) / PureTech
Safety and Efficacy of KarXT (Xanomeline () - Mar 10, 2023 - Abstract #SIRS2023SIR_774; P2, P3 Study data arebeing analyzed and will be available at the time of the meeting. Baseline demographics, the resultsfrom primary and secondary efficacy outcomes, and the safety and tolerability of KarXT will bepresented.Discussion KarXT has the potential to be the first in a new class of treatments for individuals withschizophrenia based on muscarinic receptor agonism and a promising alternative to directdopamine D2 receptor antagonists.
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The Role of Muscarinic M1 and M4 Muscarinic Receptors inCognitive Performance () - Mar 10, 2023 - Abstract #SIRS2023SIR_430; P2 Baseline demographics, the resultsfrom primary and secondary efficacy outcomes, and the safety and tolerability of KarXT will bepresented.Discussion KarXT has the potential to be the first in a new class of treatments for individuals withschizophrenia based on muscarinic receptor agonism and a promising alternative to directdopamine D2 receptor antagonists. KarXT (xanomeline
- |||||||||| xanomeline/trospium (KarXT) / PureTech
The Potential Role of the M1/M4 Muscarinic Receptor AgonistKarXT in the Treatment of Cognitive Impairment in Patients withSchizophrenia () - Mar 10, 2023 - Abstract #SIRS2023SIR_427; P2, P3 These findings suggest that drugs targeting M1/M4 muscarinic receptorsmay have procognitive effects. Further development of KarXT and other similarly acting therapeuticagents is warranted.KeywordKeywordsSchizophreniaKarXTXanomelineCognitionMuscarinic agonistsPoster Award NoPlease list all co-authors for this poster submission.* Presenting AuthorFirst Name Last Name AffiliationPhilip * Harvey * Leonard M. Miller School ofMedicine, University of MiamiColin Sauder Karuna TherapeuticsSamantha E. Yohn Karuna TherapeuticsElizabeth Baker Cambridge CognitionFrancesca Cormack Cambridge CognitionAndrew C. Miller Karuna TherapeuticsStephen K. Brannan Karuna TherapeuticsSteven M. Paul Karuna Therapeutics2Consent of Release of Rights I have read and agree to the above terms and conditions.
- |||||||||| xanomeline/trospium (KarXT) / PureTech
Safety and Efficacy of Karxt (xanomeline () - Mar 10, 2023 - Abstract #SIRS2023SIR_413; Rates of serious TEAEs were similarwith KarXT and placebo (2%, each group); no serious TEAEs were determined to be drug related.The most common TEAEs (>5%) with KarXT were all mild to moderate in severity and includedconstipation, dyspepsia, nausea, vomiting, headache, blood pressure increases, dizziness,gastroesophageal reflux disease, abdominal discomfort, and diarrhea. KarXT was not associatedwith weight gain, Parkinsonism, dystonia, akathisia, prolactin elevation, or sedation, which arecommon AEs of current antipsychotic medications.Discussion KarXT has the potential to be the first in a new class of treatments for patients withschizophrenia and a promising alternative to postsynaptic dopamine D2 receptor antagonists.KeywordKeywordsKarXTxanomelinemuscarinic receptor agonistsAcute psychosisAdult schizophreniaPoster Award NoPlease list all co-authors for this poster submission.* Presenting AuthorFirst Name Last Name AffiliationChristoph * Correll * The Zucker Hillside HospitalAndrew Miller Karuna TherapeuiticsSharon Sawchak Karuna TherapeuticsInder Kaul Karuna TherapeuticsSteven M Paul Karuna TherapeuticsStephen Brannan Karuna TherapeuticsConsent of Release of Rights I have read and agree to the above terms and conditions.
- |||||||||| Journal: Long-term functional regeneration of radiation-damaged salivary glands through delivery of a neurogenic hydrogel. (Pubmed Central) - Dec 22, 2022
However, we found that mimicking cholinergic muscarinic input via sustained local delivery of a cevimeline-alginate hydrogel was sufficient to regenerate innervated acini and retain physiological saliva secretion at nonirradiated levels over the long term (>3 months). Thus, we reveal a previously unknown regenerative approach for restoring epithelial organ structure and function that has extensive implications for human patients.
- |||||||||| Tectin (tetrodotoxin) / CK Life Sci
Preclinical, Journal: Hypotonicity-Induced Increase in Duodenal Mucosal Permeability Is Regulated by Cholinergic Receptors in Rats. (Pubmed Central) - Nov 28, 2022 Thus, we reveal a previously unknown regenerative approach for restoring epithelial organ structure and function that has extensive implications for human patients. A complex enteric intramural excitatory neural reflex involving both nicotinic and muscarinic receptor subtypes mediates an increase in mucosal permeability induced by luminal hypotonicity.
- |||||||||| Miostat (carbachol) / Novartis
Journal: Cholinergic signaling impairs cardiomyocyte cohesion. (Pubmed Central) - Oct 26, 2022 This comprehensive analysis paves the way for re-examination of cortical DRD2 functions and treatments in psychomotor disorders. Our results demonstrate that cholinergic signaling antagonizes the positive effect of adrenergic signaling on cardiomyocyte cohesion and thus causes negative adhesiotropy independent of PG phosphorylation.
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