Brain penetration of ketamine: Intranasal delivery VS parenteral routes of administraion

Naidoo, V.G.; Mdanda, Sipho; Ntshangase, Sphamandla; Naicker, Tricia; Kruger, Hendrik G.; Govender, Thavendran; Naidoo, Panjasaram; Baijnath, Sooraj

doi:10.1016/j.jpsychires.2019.02.003

Cited by 14 publications

(4 citation statements)

References 18 publications

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“…Even though direct entry into the brain has been described for other coronaviruses 143 and Varga et al found evidence of direct SARS‐CoV‐2 infection of En cells and diffuse En inflammation 136,138 . Since nanoparticle delivery to the brain occurs through direct intranasal delivery, drugs introduced into the nasal cavity can reach the brain either via the olfactory bulbs and the trigeminal nerve or via the lymphatic system 190,191 . This could, therefore, most likely also be a route for SARS‐CoV‐2 infection, seen that viral RNA was detected in olfactory neuronal cells in both animal models and humans.…”

Section: Pathophysiology Of Covid‐19mentioning

confidence: 99%

“…136,138 Since nanoparticle delivery to the brain occurs through direct intranasal delivery, drugs introduced into the nasal cavity can reach the brain either via the olfactory bulbs and the trigeminal nerve or via the lymphatic system. 190,191 This could, therefore, most likely also be a route for SARS-CoV-2 infection, seen that viral RNA was detected in olfactory neuronal cells in both animal models and humans. Autopsy results from patients with severe COVID-19 revealed a low level of SARS-CoV-2 invasion across the cribriform plate into the olfactory bulb within the cranium.…”

Section: Covid-19mentioning

confidence: 99%

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Pathogenesis of COVID‐19 described through the lens of an undersulfated and degraded epithelial and endothelial glycocalyx

et al. 2021

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The glycocalyx surrounds every eukaryotic cell and is a complex mesh of proteins and carbohydrates. It consists of proteoglycans with glycosaminoglycan side chains, which are highly sulfated under normal physiological conditions. The degree of sulfation and the position of the sulfate groups mainly determine biological function. The intact highly sulfated glycocalyx of the epithelium may repel severe acute respiratory syndrome‐related coronavirus 2 (SARS‐CoV‐2) through electrostatic forces. However, if the glycocalyx is undersulfated and 3‐O‐sulfotransferase 3B (3OST‐3B) is overexpressed, as is the case during chronic inflammatory conditions, SARS‐CoV‐2 entry may be facilitated by the glycocalyx. The degree of sulfation and position of the sulfate groups will also affect functions such as immune modulation, the inflammatory response, vascular permeability and tone, coagulation, mediation of sheer stress, and protection against oxidative stress. The rate‐limiting factor to sulfation is the availability of inorganic sulfate. Various genetic and epigenetic factors will affect sulfur metabolism and inorganic sulfate availability, such as various dietary factors, and exposure to drugs, environmental toxins, and biotoxins, which will deplete inorganic sulfate. The role that undersulfation plays in the various comorbid conditions that predispose to coronavirus disease 2019 (COVID‐19), is also considered. The undersulfated glycocalyx may not only increase susceptibility to SARS‐CoV‐2 infection, but would also result in a hyperinflammatory response, vascular permeability, and shedding of the glycocalyx components, giving rise to a procoagulant and antifibrinolytic state and eventual multiple organ failure. These symptoms relate to a diagnosis of systemic septic shock seen in almost all COVID‐19 deaths. The focus of prevention and treatment protocols proposed is the preservation of epithelial and endothelial glycocalyx integrity.

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Section: Pathophysiology Of Covid‐19mentioning

confidence: 99%

Section: Covid-19mentioning

confidence: 99%

Pathogenesis of COVID‐19 described through the lens of an undersulfated and degraded epithelial and endothelial glycocalyx

et al. 2021

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“…[8]. U szczurów, które otrzymały ketaminę w dawce 15 mg/kg masy ciała maksymalne stężenie związku w mózgu wynosiło 61,8, 354,1 i 77,8 ng/g tkanki, odpowiednio po podaniu dożołądkowym, dootrzewnowym i donosowym [9]. Ketamina ulega stereoselektywnej biotransformacji do różnych metabolitów, w tym norketaminy, dwóch diastereoizomerów hydroksyketaminy, sześciu diastereoizomerów hydroksynorketaminy oraz dehydronorketaminy; niektóre z nich są aktywne biologicznie [10].…”

Section: Parametry Farmakokinetyczne Ketaminyunclassified

Ketamine – a prototype of rapidly acting antidepressant drugs

Zawilska¹,

Kacprzak²

2019

Farm Pol.

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“…The side effects and abuse liability associated with the parent drug have motivated the pursuit of K-like alternatives such as enantio-pure, sustained-release or active metabolite formulations in order to circumvent the current limitations placed on antidepressant therapy with S -K, which is available only for supervised administration at certified health care providers, and rac -K, the off-label infusion of which is restricted to in-patients [6,7,8]. Regrettably, the nature and precise mechanism of action responsible for rapid-onset yet sustained antidepressant effects is still being debated [9].…”

Section: Introductionmentioning

confidence: 99%

Subcritical Fluid Chromatography at Sub-Ambient Temperatures for the Chiral Resolution of Ketamine Metabolites with Rapid-Onset Antidepressant Effects

et al. 2019

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Chiral metabolites of ketamine exerting rapid-onset yet sustained antidepressant effects may be marketed directly in the future, but require chemo- and enantio-selective chromatographic methods for quality assurance and control. The chromatographic behavior of S-/R-ketamine, S-/R-norketamine, S-/R-dehydronorketamine, and (2R,6R)-/(2S,6S)-hydroxynorketamine in supercritical fluid chromatography (SFC) was investigated computationally and experimentally with the aim of identifying problematic pairs of enantiomers and parameters for chiral resolution. Retention on three different polysaccharide-based chiral stationary phases (Lux Amylose-2, i-Amylose-3, and i-Cellulose-5) provided new information on the significance of halogen atoms as halogen bond donors and hydrogen bond acceptors for enantioselectivity, which could be corroborated in silico by molecular docking studies. Modifiers inversely affected enantioselectivity and retention. Methanol yielded lower run times but superior chiral resolution compared to 2-propanol. Lower temperatures than those conventionally screened did not impair phase homogeneity but improved enantioresolution, at no cost to reproducibility. Thus, sub-ambient temperature subcritical fluid chromatography (SubFC), essentially low-temperature HPLC with subcritical CO2, was applied. The optimization of the SubFC method facilitated the chiral separation of ketamine and its metabolites, which was applied in combination with direct injection and online supercritical fluid extraction to determine the purity of pharmaceutical ketamine formulations for proof of concept.

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Brain penetration of ketamine: Intranasal delivery VS parenteral routes of administraion

Cited by 14 publications

References 18 publications

Pathogenesis of COVID‐19 described through the lens of an undersulfated and degraded epithelial and endothelial glycocalyx

Pathogenesis of COVID‐19 described through the lens of an undersulfated and degraded epithelial and endothelial glycocalyx

Ketamine – a prototype of rapidly acting antidepressant drugs

Subcritical Fluid Chromatography at Sub-Ambient Temperatures for the Chiral Resolution of Ketamine Metabolites with Rapid-Onset Antidepressant Effects

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