NT0502 Remains on Track to Enter the Clinic in 1H 2020: NT0502 is a new chemical entity and a selective muscarinic receptor antagonist
that will utilize the same microparticle technology used in the Company's four approved products.
KarXT (Karuna-Xanomeline-Trospium), Karuna's lead product candidate for the treatment of psychosis in schizophrenia, consists of xanomeline, a novel muscarinic acetylcholine receptor agonist that has demonstrated efficacy in placebo-controlled human trials in schizophrenia and Alzheimer's disease, and trospium chloride, an FDA-approved and well-established muscarinic receptor antagonist
that has been shown not to enter the central nervous system.
The label update is based on data from the landmark InforMing the PAthway of COPD Treatment (IMPACT) study which showed Trelegy Ellipta was superior to both the ICS/LABA Relvar/Breo Ellipta (FF/VI) and long-acting muscarinic receptor antagonist
(LAMA)/LABA Anoro Ellipta (UMEC/VI) in patients with moderate to severe COPD on multiple clinically important endpoints, including reducing exacerbations and improving lung function and health related quality of life.
The expanded indication for the once-daily single inhaler triple therapy is to allow use by patients not adequately treated by a long-acting muscarinic receptor antagonist
and long-acting beta-2-agonist.
The expanded indication for the once-daily single inhaler triple therapy would enable use by patients not adequately treated by a long-acting muscarinic receptor antagonist
and long-acting beta2-agonist.
Atropine, a nonspecific muscarinic receptor antagonist
, is a potent cycloplegic and was initially used for myopia control on the premise that excessive ocular accommodation was the cause of myopia progression.
Afterward, DRC for ACh were performed in vessels pre-incubated for 30 min with Atropine (At, [10.sup.-5] M), an muscarinic receptor antagonist
, and indomethacin (IND, [10.sup.-5] M), an unspecific inhibitor of cyclooxygenases.
Hydrochlorothiazide (HCTZ; thiazide diuretic), acetazolamide (ACTZ; carbonic anhydrase inhibitor), ouabain octahydrate (sodium potassium ATPase inhibitor), N-[omega]-Nitro-L-arginine methyl ester (L-NAME; NO synthase inhibitor), icatibant acetate (HOE-140; [B.sub.2] bradykinin receptor antagonist), indometacin (cyclooxygenase inhibitor), atropine (muscarinic receptor antagonist
), and captopril (angiotensin converting enzyme inhibitor), were obtained from Sigma-Aldrich Chemical Co.
The nonselective muscarinic receptor antagonist
atropine blocked the stimulatory effect of taurine (10-60 mM) on the contractile amplitude of isolated jejunal segments in LCS induced by low [Ca.sup.2+] (1.25 mM) Krebs buffer.
Pretreatment of DSM preparations with the muscarinic receptor antagonist
atropine [10.sup.-6] M was added the medium.
Oxybutynin, a non-selective muscarinic receptor antagonist
, and darifenacin, selective for M[sub.3] receptors, have been demonstrated to modulate bladder afferent activity, both in C fibres and Adelta fibres.[sup.5] Such an effect may be an important mechanism of action for antimuscarinics.
Tiotropium bromide (Spiriva), a muscarinic receptor antagonist
, is a long-acting bronchodilator.