In vitro and in vivo comparison of two non-peptide tachykinin NK3 receptor antagonists: Improvements in efficacy achieved through enhanced brain penetration or altered pharmacological characteristics.

@article{Dawson2010InVA,
  title={In vitro and in vivo comparison of two non-peptide tachykinin NK3 receptor antagonists: Improvements in efficacy achieved through enhanced brain penetration or altered pharmacological characteristics.},
  author={Lee A. Dawson and Christopher James Langmead and Adeshola Dada and Jeannette M. Watson and Zining Wu and Ra{\'u}l de la Flor and Gareth A. Jones and Jane E. Cluderay and Eric Southam and Graham S Murkitt and Mark D Hill and Declan Jones and Ceri H. Davies and Jim J. Hagan and Paul W Smith},
  journal={European journal of pharmacology},
  year={2010},
  volume={627 1-3},
  pages={
          106-14
        }
}
Tachykinin neurokinin 3 receptor antagonists: a patent review (2005 – 2010)
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This review article discusses the latest medicinal chemistry strategies used to derive novel NK3 receptor antagonists which have been patented during the period 2005 – 2010.
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A necessity for molecular tools to understand the biological role of this class endogenous peptides and their receptors prompted the scientific community to design ligands displaying either agonist and antagonist activity at the three main neurokinin receptors, called NK1, NK2 and NK3.
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The emerging structural biology and its use in the design of molecules with increased structural diversity and predictable receptor pharmacology are discussed and the potential therapeutic utility of NK3 receptor targeted ligands are evaluated.
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TLDR
Results of the trial do not support a role for the NK3 antagonist AZD2624 as a therapeutic treatment for acute schizophrenia when used as monotherapy.
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TLDR
There is a wide spectrum of therapeutic uses of Kiss-1 and NKB agonists, including the management of infertility, treatment for PCOS, functional hypothalamic amenorrhea or postmenopausal vasomotor symptoms, as well as contraceptive issues.
Population Pharmacokinetic and Pharmacodynamic Modeling of AZD4901 and Simulation to Support Dose Selection for the Phase 2a Study
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Population PK and PK/PD analyses demonstrated that AZD4901 40 mg BID is a better dosing strategy to more consistently suppress testosterone during the entire dosing interval, and Consequently, 40mg BID dosing was suggested in a phase 2a trial in females with polycystic ovary syndrome, and the trial resulted in a positive outcome as shown by significant testosterone decrease compared to placebo.
The "Cyclopropyl Fragment" is a Versatile Player that Frequently Appears in Preclinical/Clinical Drug Molecules.
  • T. Talele
  • Chemistry, Biology
    Journal of medicinal chemistry
  • 2016
TLDR
The cyclopropyl ring addresses multiple roadblocks that can occur during drug discovery such as enhancing potency, reducing off-target effects, and improving the properties of drugs containing it.

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Data demonstrate that talnetant is a selective, competitive, brain-penetrant NK3 receptor antagonist with the ability to modulate mesolimbic and mesocortical dopaminergic neurotransmission and hence support its potential therapeutic utility in the treatment of schizophrenia.
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