Centhaquin attenuates hyperalgesia and non-evoked guarding in a rat model of postoperative pain primarily through α 2B -adrenoceptors

Leonard, Mary G.; Jung, Shawn; Andurkar, Shridhar V.; Gulati, Anil

doi:10.1016/j.ejphar.2016.07.016

Cited by 5 publications

(2 citation statements)

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“…The second important finding was a difference in the responses of naïve rats to IT alpha antagonists compared to those of CCI rats. Both male and female naïve rats showed the opposing effects of α 1 - and α 2 -adrenoceptors similar to those we have reported previously in females (Holden and Naleway, 2001; Jeong and Holden, 2009), and that others have reported for male rats with α 2 -adrenoceptor involvement with post-operative pain (Leonard et al, 2016). In the naïve model, stimulation of the LH produces antinociception in both male and female rats, albeit with carbachol dose differences (Holden et al, 2014), indicating that the net effect of opposing alpha-adrenoceptor involvement following an acute thermal stimulus is antinociception.…”

Section: Discussionsupporting

confidence: 90%

Pain condition and sex differences in the descending noradrenergic system following lateral hypothalamic stimulation

et al. 2020

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Section: Discussionsupporting

confidence: 90%

Pain condition and sex differences in the descending noradrenergic system following lateral hypothalamic stimulation

et al. 2020

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“…Large arteries like the aorta have a high amount of α2A, whereas α2B is abundant in peripheral veins and scarcely in arteries, contributing to most venoconstriction. The dose range of 0.015–0.02 mg/kg body weight centhaquine (CQ) acts on the α2B ARs and induces constriction in most of the veins along with small arteries, which helps in the return of venous pooled blood to the heart ( Gulati et al, 2013a ; Gulati et al, 2012a ; Kontouli et al, 2019 ; Lavhale et al, 2013 ; Leonard et al, 2016 ; O'Donnell et al, 2016a ; O'Donnell et al, 2016b ; Papapanagiotou et al, 2016 ; Reniguntala et al, 2015 ; Gulati et al, 2020 ). It leads to a significant improvement in CO and MAP after resuscitation ( Figure 1 ).…”

Section: Development Of Centhaquine An α-2 Agonist As a Resuscitative...mentioning

confidence: 99%

Role of adrenergic receptors in shock

Geevarghese¹,

Patel

Gulati

et al. 2023

Front. Physiol.

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Shock is a severe, life-threatening medical condition with a high mortality rate worldwide. All four major categories of shock (along with their various subtypes)—hypovolemic, distributive, cardiogenic, and obstructive, involve a dramatic mismatch between oxygen supply and demand, and share standard features of decreased cardiac output, reduced blood pressure, and overall hypoperfusion. Immediate and appropriate intervention is required regardless of shock type, as a delay can result in cellular dysfunction, irreversible multiple organ failure, and death. Studies have shown that dysfunction and downregulation of adrenergic receptors (ARs) are often implicated in these shock conditions; for example, their density is shown to be decreased in hypovolemic and cardiogenic shock, while their reduced signaling in the brain and vasculature decrease blood perfusion and oxygen supply. There are two main categories of ARs, α, and β, each with its subtypes and distributions. Our group has demonstrated that a dose of .02 mg/kg body wt of centhaquine (CQ) specifically activates α2B ARs on venous circulation along with the central α2A ARs after hypovolemic/hemorrhagic shock. Activating these receptors by CQ increases cardiac output (CO) and reduces systemic vascular resistance (SVR), with a net increase in blood pressure and tissue perfusion. The clinical trials of CQ conducted by Pharmazz Inc. in India have demonstrated significantly improved survival in shock patients. CQ improved blood pressure and shock index, indicating better blood circulation, and reduced lactate levels in the blood compared to in-use standard resuscitative agents. After successful clinical trials, CQ is being marketed as a drug (Lyfaquin®) for hypovolemic/hemorrhagic shock in India, and United States FDA has approved the phase III IND application. It is anticipated that the phase III trial in the United States will begin in 2023. Thus, we have demonstrated that α2 ARs could be suitable targets for treating or managing hypovolemic/hemorrhagic shock. Further understanding of ARs in shock would help find new potential pharmacological targets.

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The analgesic effects of ulinastatin either as a single agent or in combination with sufentanil: A novel therapeutic potential for postoperative pain

Guo

Tang

Wang

et al. 2021

European Journal of Pharmacology

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Centhaquin attenuates hyperalgesia and non-evoked guarding in a rat model of postoperative pain primarily through α 2B -adrenoceptors

Cited by 5 publications

References 22 publications

Pain condition and sex differences in the descending noradrenergic system following lateral hypothalamic stimulation

Pain condition and sex differences in the descending noradrenergic system following lateral hypothalamic stimulation

Role of adrenergic receptors in shock

The analgesic effects of ulinastatin either as a single agent or in combination with sufentanil: A novel therapeutic potential for postoperative pain

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