The Neurokinin-1 Receptor Antagonist Orvepitant Is a Novel Antitussive Therapy for Chronic Refractory Cough

Smith, Jaclyn A.; Allman, David; Badri, Huda; Miller, Robert T.; Morris, Jonathan; Satia, Imran; Wood, Andrew; Trower, Michael K.

doi:10.1016/j.chest.2019.08.001

Cited by 70 publications

(50 citation statements)

References 34 publications

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“…Cough medicines have evolved over centuries to maximize the placebo effect by being formulated as sweet viscous syrups and this evolution is still in progress today as pharmaceutical companies utilize new flavors and sensations to increase the impact of their OTC cough medicines. There is an ongoing research effort to develop new antitussive medicines and most of these involve clinical trials on actives in tablet form [4,59]. However, if these new active agents are eventually used commercially for the treatment of cough, the efficacy of the cough medicine would be greatly enhanced by formulating the medicine as a sapid sweet syrup in order to utilize a large placebo effect of treatment in addition to any pharmacological effect of the medicine.…”

Section: How Can the Placebo Effect Be Utilized In The Development Ofmentioning

confidence: 99%

The Powerful Placebo Effect in Cough: Relevance to Treatment and Clinical Trials

Eccles

2019

Lung

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Interest in the placebo effect of medicines has developed from the use of placebo treatments as controls in clinical trials into a whole new area of research around how placebos fit into a psychosocial model of therapeutics. The large placebo effect associated with cough medicines is both a problem and an opportunity for researchers: a problem for clinical trials on new actives as the active must beat the large placebo effect, and an opportunity for harnessing the placebo effect to produce effective cough medicines without any pharmacologically active ingredient. This review discusses the mechanisms associated with the placebo effect of cough medicines and distinguishes between a 'perceived placebo effect' and a true 'placebo effect'. The efficacy of sweeteners in cough syrups is discussed as well as viscosity, mucoadhesion, and flavoring. The complexity of modern cough medicines is demonstrated by an example of a medicine which contains one active ingredient, and eighteen excipients which provide a complex and intense sensory experience to enhance the placebo effect and complement the pharmacological activity of the medicine.

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Section: How Can the Placebo Effect Be Utilized In The Development Ofmentioning

confidence: 99%

The Powerful Placebo Effect in Cough: Relevance to Treatment and Clinical Trials

Eccles

2019

Lung

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“…The efficacy and safety of orvepitant, a brain-penetrant NK1R antagonist, in an open-label study in patients with chronic refractory cough were established. Orvepitant resulted in a significant and sustained improvement in objective cough frequency, severity visual analogue scale (VAS), and quality of life; appeared safe, and merits further clinical investigation (Smith et al 2019).…”

Section: Coughmentioning

confidence: 99%

Itch and Cough – Similar Role of Sensory Nerves in Their Pathogenesis

Pecova

Kocan²,

Vyšehradský³

et al. 2020

Physiol Res

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Itch is the most common chief complaint in patients visiting dermatology clinics and is analogous to cough and also sneeze of the lower and upper respiratory tract, all three of which are host actions trying to clear noxious stimuli. The pathomechanisms of these symptoms are not completely determined. The itch can originate from a variety of etiologies. Itch originates following the activation of peripheral sensory nerve endings following damage or exposure to inflammatory mediators. More than one sensory nerve subtype is thought to subserve pruriceptive itch which includes both unmyelinated C-fibers and thinly myelinated Aδ nerve fibers. There are a lot of mediators capable of stimulating these afferent nerves leading to itch. Cough and itch pathways are mediated by small-diameter sensory fibers. These cough and itch sensory fibers release neuropeptides upon activation, which leads to inflammation of the nerves. The inflammation is involved in the development of chronic conditions of itch and cough. The aim of this review is to point out the role of sensory nerves in the pathogenesis of cough and itching. The common aspects of itch and cough could lead to new thoughts and perspectives in both fields.

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“…20 Other antitussive targets include the neurokinin-1, TRPV4, and alpha-7 nicotinic receptors. [58][59][60] Further studies of thalidomide and similar drugs are also warranted.…”

Section: Future Directionsmentioning

confidence: 99%