Table 2.
List of important centhaquine studies
| Sl. # | Study, year | Species (n) | Aim of the study | Brief study details and main findings | Proposed mechanism of action |
|---|---|---|---|---|---|
| 1 | Bhatnagar et al., [66] 1985 | Rabbit | Effect of centhaquine on spontaneous and evoked norepinephrine release from isolated perfused heart | Centhaquine affects NE release from the rabbit heart. Centhaquine 0.1, 1.0, and 10.0 µg/mL initially increased then inhibited spontaneous NE output. It significantly suppressed NE release evoked by KCl, DMPP, and acetylcholine but did not affect NE release induced by tyramine or amphetamine. Findings suggest that centhaquine primarily inhibits neuronal NE release | The biphasic effect of centhaquine on NE concentration (initial increase and later decrease) could be because centhaquine predominantly inhibits the neuronal NE release but does not affect NE release from peripheral nerves |
| 2 | Srimal et al., [88] 1990 | Rat (55) and cat (no. of exp. 169) | Pharmacological studies on 2-(2-(4-(3-methylphenyl)-1-piperazinyl)ethyl) quinoline (centhaquin). I. Hypotensive activity | Centhaquine lowered BP and reduced HR in a dose-dependent manner (0.01–1.0 mg/kg IV or 1.0–2.5 mg/kg intraduodenally) in cats. The hypotensive effect was insignificant in spinal transected cats but more marked in deafferented and vagotomized animals. Localization of centhaquine to brain by intravertebral arterial injection (5–10 µg) or by topical application to the exposed ventral surface of the medulla or floor of the fourth ventricle caused hypotension and bradycardia and reduced the excitability of the vasomotor loci. It was also effective in rats after single and multiple dosing | Centhaquine seems to act centrally to reduce BP |
| 3 | Gulati et al., [67] 1991 | Rat (10) | Effect of repeated administration of centhaquine, a centrally acting hypotensive drug, on adrenergic, cholinergic (muscarinic), dopaminergic, and serotonergic receptors in brain regions of rat | Oral administration of centhaquine 0.1 mg/kg for 2 mo in rats led to changes in central α-adrenergic, dopaminergic, and 5-HT1 receptors and a significant decrease in mean BP. Centhaquine had no effect on Bmax or Kd values of 3H-dihydroergocryptine binding in the cerebral cortex and corpus striatum, it significantly increased Bmax in the hypothalamus (52%) and medulla (86%) without altering Kd values. Centhaquine did not affect β-adrenergic, muscarinic cholinergic, or 5-HT2 receptor binding in any brain region. However, it reduced the Bmax of 3H-spiroperidol binding to dopaminergic receptors in the cortex (25%) but had no effect in other regions. Similarly, centhaquine had no impact on 5-HT1 receptor binding in most regions but increased Bmax by 41% in the medulla without altering Kd values | Centhaquine influences central neurotransmitter receptor systems, particularly in the medulla and hypothalamus, which may contribute to its hypotensive effects |
| 4 | Gulati et al., [68] 1993 | Rat (24) | Central serotonergic uptake mechanisms in hypertensive rats: effects of clonidine and centhaquine | The study examined the binding of [3H]paroxetine, a ligand for 5-HT-uptake sites, in different brain regions of normotensive WKY rats and SHR. SHR exhibited a significant 27.16% reduction in [3H]paroxetine Bmax in the midbrain compared with WKY; Kd remained unchanged. No significant differences in Bmax or Kd in other brain regions. Study also assessed the effects of the hypotensive agents clonidine and centhaquine on [3H]paroxetine binding. Clonidine had no effect; centhaquine displaced [3H]paroxetine binding in a concentration-dependent manner, similar to imipramine, a known 5-HT uptake inhibitor. Centhaquine was more potent than imipramine in displacing paroxetine, with an IC50 value 10 times lower in the cerebral cortex and 4 times lower in the brainstem | By inhibiting 5-HT uptake, centhaquine may enhance serotonergic signaling, which could play a role in its hypotensive effects through central modulation of sympathetic activity |
| 5 | Gulati et al. , [69] 2011 | Rat (50) | Effect of Centhaquin on norepinephrine requirement for maintaining blood pressure and improving survival in hemorrhage rats | The study evaluated the effect of centhaquine on NE requirements for maintaining a MAP of 70 mmHg in severely hemorrhaged rats. Blood lactate was significantly lower with centhaquine (1.65 ± 0.23 mmol/L) than with NS (4.10 ± 1.02 mmol/L, p = 0.041) at 60 min after resuscitation. The NE required to maintain MAP was substantially lower with centhaquine (17.5 µg) than with NS (175 µg) during the first 60 min, indicating centhaquine's potential to improve resuscitation efficiency | Centhaquine decreases the requirement of NE in hemorrhaged rats, possibly due to improved vascular responsiveness |
| 6 | Andurkar et al., [70] 2011 | Mouse (32) | Assessment of the analgesic effect of centhaquine in mouse tail flick and hot-plate tests | Centhaquine was evaluated for its analgesic and hypothermic effects in mice and its potential to enhance morphine analgesia. In tail flick and hot-plate tests, centhaquine demonstrated dose-dependent analgesia, partially blocked by yohimbine, idazoxan, and naloxone, indicating involvement of α(2)-adrenergic, imidazoline, and opioid receptors, while endothelin ETA antagonists BQ123 and sulfisoxazole had no effect. Centhaquine did not potentiate morphine analgesia. Additionally, centhaquine induced mild hypothermia, which was unaffected by any antagonists. This study provides the first evidence of centhaquine’s analgesic properties, mediated by adrenergic, imidazoline, and opioid receptors, with no role for endothelin ETA receptors | The possible mechanism underlying centhaquine’s analgesic effects involves its interaction with α(2)-adrenergic, imidazoline, and opioid receptors |
| 7 | Briyal et al., [71] 2012 | Pregnant rats (16) and neonatal rats (48) | Effect of repeated administration of centhaquine in pregnant rats on postnatal development and expression of endothelin receptors in the brain, heart or kidney of rat pups | The study examined the effects of centhaquine on pregnant and postnatal rats. Pregnant rats in both vehicle and centhaquine groups showed steady weight gain, and centhaquine had no impact on ETA receptor expression in the heart and kidney but significantly increased its expression in the brain of postpartum rats. ETB receptor expression remained unchanged. In postnatal rats, body and organ weights (brain, kidney, heart) increased proportionally with age and were unaffected by centhaquine. ETA receptor expression was similar between groups; ETB receptor expression significantly decreased (p <0.001) by day 28 in both groups | Effect of centhaquine on ETA receptor expression in the brain of postpartum rats may indicate its potential role in neuroadaptive response in the postpartum phase; however, no effects on ETA and ETB expressions in rat pups may spare their postnatal development |
| 8 | Gulati et al. [57], 2012 | Rat (36) | Study of the resuscitative effect of Centhaquine with hypertonic saline in hemorrhaged rats | HS reduced blood lactate levels and improved CO in hemorrhaged rats. When combined with centhaquine, it led to a greater reduction in blood lactate and a more significant increase in MAP and CO. At 250 min after resuscitation, survival was 0 in the HS group but 0.8 in the centhaquine group, highlighting its superior efficacy | The enhanced efficacy of centhaquine combined with HS may be attributed to its synergistic effects on CV function and tissue perfusion, ultimately contributing to higher survival rates in hemorrhaged rats |
| 9 | Gulati et al. [72], 2012 | Rat | Role of alpha-adrenoceptor in hemorrhaged rats after resuscitative with centhaquine | This study investigated the mechanism of action of centhaquine, hypothesizing that its resuscitative effects are mediated through α2-ARs. Using pressure–volume loop analysis and blood gas measurements, centhaquine 0.05 mg/kg reduced blood lactate levels, improved CO, and stabilized BP. The resuscitative effects were significantly antagonized by α2-AR blockers, yohimbine and atipamezole, confirming the involvement of α2 receptors in centhaquine’s mechanism of action | The resuscitative effect of centhaquine may be attributed to its action on α2-ARs, which play a key role in cardiovascular regulation |
| 10 | Gulati et al. [56], 2013 | Rat (12) | Efficacy of centhaquine as a small volume resuscitative agent in severely hemorrhaged rats | Centhaquine significantly reduced blood lactate levels and improved CO and MAP in hemorrhaged rats compared with HS. MAP dropped to 35 mmHg within 55 ± 6 min in HS-treated rats and within 161 ± 14 min in centhaquine-treated rats. Survival time after fresh blood administration was 79 ± 7 min in the vehicle-treated group and 105 ± 9 min with centhaquine. Overall survival time was 134 ± 12 min with HS and 266 ± 16 min with centhaquine, indicating improved survival with centhaquine | Centhaquine mediated improved CO, better MAP stability, and reduced lactate levels compared with HS; could be pivotal for better resuscitative effects of centhaquine in hemorrhaged rats |
| 11 | Lavhale et al. [59], 2013 | Rat (32) | Resuscitative effect of centhaquine after hemorrhagic shock in rats | Centhaquine 0.017 and 0.05 mg/kg led to a marked improvement in survival time (291 ± 57 and 387 ± 39 min, respectively) compared with LR-100 (78 ± 10 min) in hemorrhaged rats. It also significantly reduced blood lactate levels and increased mean MAP by 55% and 59%; LR-100 led to a 29% decrease. Centhaquine increased CO by 260% and 180% and decreased SVR more effectively than LR-100. Compared with LR-300, centhaquine 0.05 mg/kg demonstrated superior efficacy in improving survival, increasing CO, and resuscitating hemorrhaged rats, highlighting its potential as an effective resuscitative agent for hemorrhagic shock | Centhaquine 0.05 mg/kg mediated significant improvement in CO and MAP and decreased SVR in hemorrhaged rats; this could explain its better resuscitative effects over LR-100 or LR-300 |
| 12 | Bhalla et al. [73], 2013 | Mouse | Study of signaling pathways for centhaquine-mediated antinociception in mice | This study investigated the role of α2-AR subtypes in centhaquine-induced antinociception. Antinociceptive effects were blocked by BRL-44408 (α2A-AR antagonist) and imiloxan (α2B-AR antagonist) but remained unaffected by JP-1302 (α2C-AR antagonist). These findings indicate that centhaquine mediates its antinociceptive effects through α2A-AR and α2B-AR, but not α2C-AR, marking the first report of this specific receptor involvement | α2-agonism of centhaquine may be mediated through α2A-AR and α2B-AR but not by α2C-AR |
| 13 | Kachanov et al. [74], 2014 | Rat (16) | Role of centhaquine in resuscitation of endotoxic (septic) shock in rats | Centhaquine 0.05 mg/kg was evaluated for its effects on survival and hemodynamic performance in a rat model of septic shock induced by IV LPS 20 mg/kg. Centhaquine significantly increased HR (26 +/− 4% vs 14 +/− 3%, p = 0.016) and CO (70 +/− 15% vs 27 +/− 13%, p = 0.03) compared to control treatment. Also, a trend toward increased SV in centhaquine group compared to the control group was seen; however, it did not improve survival time (161 ± 16 vs. 152 ± 20 min, p > 0.05), significantly. Thus, centhaquine could be supportive with ement of cardiac performance; centhaquine did not significantly affect mortality in this septic shock model | The possible mechanism by which centhaquine 0.05 mg/kg temporarily enhances cardiac performance in septic shock may involve its role in modulating vascular tone and cardiac function. Centhaquine could provide hemodynamic support in septic shock |
| 14 | Goyal et al. [75], 2015 | Human (24) | Safety and efficacy of centhaquine as a novel resuscitative agent for hypovolemic shock | This was a single-center, randomized, DB, PC phase I trial to evaluate the safety of PMZ-2010 (centhaquine) (NCT02408731) in healthy male subjects in 6 cohorts of 4 subjects each: 3 received the active drug, 1 received placebo. The SAD cohorts began with an initial dose of 0.005 mg/kg of PMZ-2010 via IV infusion, and doses were escalated based on safety and tolerability up to 0.10 mg/kg, which was determined as the MTD. In the MAD cohorts, the initial dose was 0.10 mg/kg/day (3 × 0.033 mg/kg/day) for 2 days, escalating to 2 times the MTD (0.20 mg/kg) for 2 days. The study concluded that the MTD of PMZ-2010 in humans is 0.10 mg/kg and can be safely used for resuscitative purposes | The observed safety profile and established MTD of 0.10 mg/kg suggest that centhaquine can be used as a resuscitative agent with a favorable therapeutic window |
| 15 | Reniguntala et al. [64], 2015 | Rat (30) | Synthesis and characterization of centhaquine and its citrate salt and a comparative evaluation of their cardiovascular actions | Centhaquine causes hypotension and bradycardia at higher doses and acts as a resuscitative agent at lower doses. However, its water insolubility limits IV use. To address this, the citrate salt of centhaquine was synthesized and evaluated for CV efficacy compared with centhaquine. Centhaquine citrate was 99.8% pure and water soluble. In anesthetized male SD rats, centhaquine citrate produced a significantly greater decrease in MAP, PP, HR, CO, SV, and SW compared with centhaquine at equivalent doses (0.05, 0.15, and 0.45 mg/kg). At 0.45 mg/kg, centhaquine citrate reduced CO by 42.1% (p < 0.001) compared with a 20.9% reduction with centhaquine (p < 0.01). These findings indicate that centhaquine citrate has greater CV activity than centhaquine | The better CV effects of centhaquine citrate could be because of its better solubility, dissolution rate, and absorption in the body than centhaquine |
| 16 | O'Donnell et al. [61], 2016 | Rat (16) | Pharmacokinetics of centhaquine citrate in a rat model | A two-compartment model was used to best fit the pharmacokinetic data for centhaquine citrate. The median (IQR) values for the Ke, V, and Kcp, Kpc were 8.8 (5.2–12.8) h⁻1, 6.4 (2.8–10.4) L, 11.9 (4.6–15.0) h⁻1, and 3.7 (2.3–9.1) h⁻1, respectively. Centhaquine citrate has a short half-life and a large V, suggesting rapid clearance from the plasma and widespread tissue distribution | Pharmacokinetic profile of centhaquine citrate in rats with a combination of rapid clearance and extensive tissue distribution may contribute to its effectiveness in modulating vascular tone and tissue perfusion, particularly in hemorrhagic conditions |
| 17 | Gulati et al. , [76] 2016 | Human (24) | Human pharmacokinetics of centhaquine citrate, a novel resuscitative agent | This study aimed to determine the pharmacokinetics of PMZ-2010 (centhaquine citrate) in healthy human volunteers through a randomized, DB, PC phase I trial. Subjects received IV PMZ-2010 0.005–0.10 mg/kg, and plasma concentrations were measured at various time points up to 8 h after administration. The pharmacokinetic data were best described by a two-compartment model, with Bayesian predictions showing high accuracy (R2 = 0.94). Key pharmacokinetic parameters included a Ke of 4.1 h⁻1, V of 29.5 L, and Kcp and Kpc of 10.4 h⁻1 and 2.1 h⁻1, respectively. Results indicated that PMZ-2010 has rapid plasma elimination, and the pharmacokinetic profile aligns with previous studies in rats and dogs | The rapid clearance and distribution observed in humans may contribute to its effectiveness in clinical resuscitation protocols, where timely and efficient tissue perfusion is essential |
| 18 | O'Donnell et al. [62], 2016 | Dog (4) | Pharmacokinetics of centhaquine citrate in a dog model | The pharmacokinetic parameters of centhaquine citrate were best described using a two-compartment model. The median (IQR) values for the Ke, Vc, Vp, Kcp, and Kpc were 4.9 (4.4–5.2) h⁻1, 328.4 (304.0–331.9) L, 1000.6 (912.3–1042.4) L, 10.6 (10.3–11.1) h⁻1, and 3.2 (2.9–3.7) h⁻1, respectively. These show that centhaquine citrate has a large V and rapid elimination, which is consistent with previous pharmacokinetic studies in rats, indicating efficient tissue distribution and fast clearance from the body | The pharmacokinetic profile of centhaquine citrate in dogs with a combination of rapid clearance and extensive tissue distribution may contribute to its effectiveness in modulating vascular tone and tissue perfusion, particularly in hemorrhagic conditions |
| 19 | Papapanagiotou et al. [63], 2016 | Pig (20) | Resuscitative effect of Centhaquine in a swine model of hemorrhagic shock | Centhaquine 0.015 mg/kg was evaluated in a swine hemorrhagic shock model to assess its impact on 24-h survival, fluid requirements, and resuscitation time. 20 female pigs were subjected to controlled hemorrhagic shock and randomized into a centhaquine-treated group or a control group receiving only LR solution. Centhaquine significantly reduced the time to reach target MAP (7.10 ± 0.97 vs. 36.88 ± 3.26 min, p < 0.001) and required a lower total fluid volume for resuscitation. Survival at 24 h was 100% with centhaquine and 30% in the control group (p = 0.003). These results suggest that centhaquine enhances survival, accelerates resuscitation, and reduces fluid requirements, making it a promising adjunct for managing hemorrhagic shock | The rapid and efficient increase in MAP with enhanced survivability in the centhaquine-treated hemorrhaged pigs may be attributed to its action as an effective vasopressor, which could enhance tissue perfusion in a condition of lower fluid requirement than control |
| 20 | Kontouli et al. [58], 2019 | Pig (20) | Resuscitative effect of centhaquine and 6% hydroxyethyl starch 130/0.4 survival in a swine model of hemorrhagic shock | 20 Landrace large white pigs were subjected to hemorrhagic shock (MAP decreased to 40–45 mmHg) and randomly assigned to two groups: control (n = 10) and centhaquine group (n = 10). Both groups were given HES 130/0.4 solution for resuscitation until MAP reached 90% of baseline values. During the hemorrhagic phase, the centhaquine group showed a significantly lower HR than controls (97.6 ± 4.4 vs. 128.4 ± 3.6 bpm, p = 0.038). Time to reach target MAP was significantly shorter with centhaquine than in the control group (13.7 ± 0.4 vs. 19.6 ± 0.84 min, p = 0.012). During the resuscitation phase, MAP was significantly higher with centhaquine (89.8 ± 2.1 vs. 75.2 ± 1.6 mmHg, p = 0.02). In the observation phase, significant differences were observed in SVR and CO between the groups (SVR: 1109 ± 32.65 vs. 774.6 ± 21.82 dyn·s/cm5, p = 0.039; CO: 5.82 ± 0.31 vs. 6.9 ± 0.78 L/min, p = 0.027). Survival after 24 h was higher with centhaquine (7/10) than in the control group (2/10, p = 0.008). The centhaquine group also showed significantly lower microvascular capillary permeability and a lower wet/dry weight ratio than the control group (3.08 ± 0.6 vs. 4.8 ± 1.6, p < 0.001). Centhaquine treatment significantly improved hemodynamic parameters, reduced microvascular leakage, and enhanced survival compared with controls, suggesting its effectiveness in hemorrhagic shock resuscitation | The reduced mortality and better resuscitative outcomes in pigs with hemorrhagic shock could be because of improved hemodynamic stability, reduced microvascular leakage, and better CV support after centhaquine administration |
| 21 | Ranjan et al. [77], 2021 | Rat (15) | Effect of Centhaquine on renal blood flow and tissue protection after hemorrhagic shock and renal ischemia | A rat model of hemorrhagic shock and AKI was used to assess the effects of centhaquine on renal function. After AKI was induced through renal artery clamping and hemorrhage, rats were resuscitated with centhaquine (0.02 mg/kg) for 10 min. Centhaquine significantly improved renal blood flow (p<0.003) compared with the vehicle, despite similar MAP and HR in both groups. Blood lactate levels were lower with centhaquine (p = 0.0064) at 120 min after resuscitation. Histopathological analysis showed reduced renal damage with centhaquine. Western blot analysis revealed higher HIF-1α (p = 0.0152) and lower NGAL (p = 0.01626) levels with centhaquine; immunofluorescence showed increased HIF-1α (p < 0.045) and decreased Bax (p < 0.044) expression. Centhaquine also elevated PHD-3 expression (p < 0.0001) and reduced cytochrome C (p = 0.01429) in the renal cortex. These findings suggest that centhaquine (Lyfaquin®) enhances renal blood flow, promotes hypoxia adaptation, and reduces tissue damage and apoptosis, making it a promising candidate for AKI prevention and treatment | Centhaquine appears to protect kidneys by enhancing perfusion, reducing metabolic distress, and modulating hypoxia and apoptotic pathways after hemorrhage and AKI |
| 22 | Gulati et al. [55], 2021 | Human (45) | A multicentric, randomized, controlled phase II study to assess the resuscitative effect of centhaquine (Lyfaquin®) in hypovolemic shock patients | 50 pts were included; 45 completed the trial: control (n = 22), centhaquine (n = 23). No centhaquine-related AEs during the 28-day observation period. Baseline scores and blood parameters were similar in both groups; however, 91% of the centhaquine group and 68% of the control group required major surgery (p = 0.0526). The 28-day all-cause mortality was 0% with centhaquine and 9% in controls. The centhaquine group spent less time in the ICU and on ventilator support. The total vasopressor requirement in the first 48 h was significantly lower in the centhaquine group (3.12 ± 2.18 vs. 9.39 ± 4.28 mg), and results showed greater increases in SBP and DBP and reduced blood lactate by 1.75 ± 1.07 mmol/l on day 3. Improvements in base deficit, MODS, and ARDS were more pronounced in the centhaquine group. Centhaquine is a safe, well-tolerated, and effective resuscitative agent and improves clinical outcomes in pts with hypovolemic shock | The reduced mortality and improved clinical outcomes in pts with hypovolemic shock could be because of improved hemodynamic stability, reduced vasopressor requirements, and better CV support after centhaquine treatment |
| 23 | Gulati et al. [30], 2021 | Human (105) | A multicentric, randomized, controlled phase III study to assess the resuscitative effect of centhaquine (Lyfaquin®) in hypovolemic shock patients | This study compared the effects of centhaquine vs. standard care in pts with hypovolemic shock. Both groups received similar amounts of fluids and blood products during the first 48 h of resuscitation, but the centhaquine group required fewer vasopressors. Significant improvements were observed in SBP and PP; centhaquine led to a higher increase in these parameters than in controls, indicating improved SV. The SI was lower in the centhaquine group after 1–4 h of resuscitation. Centhaquine also led to a higher proportion of pts with improved blood lactate and base deficit levels. ARDS and MODS improved, and the centhaquine group had an 8.8% absolute reduction in 28-day all-cause mortality | The reduced mortality and better resuscitative outcomes in pts with hypovolemic shock could be because of improved hemodynamic stability, reduced vasopressor requirements, and better CV support after centhaquine treatment |
| 24 | Khanna et al. [78], 2024 | Human (12) | Effect of Centhaquine treatment on cardiac output in hypovolemic shock patients | Centhaquine, a resuscitative agent acting on α2B-ARs, was evaluated for its effect on CO in 12 pts with hypovolemic shock. The pilot study found that centhaquine significantly increased SV at 60, 120, and 300 min, and CO was significantly improved at 120 and 300 min despite decreased HR. Increased IVC diameter and LVOT-VTI at these time points indicated enhanced venous return. LVEF and LVFS did not change; MAP rose after 120 and 300 min. Positive correlations between IVC diameter and SV and between IVC diameter and MAP highlighted the role of venous return in improving hemodynamic parameters | Centhaquine’s ability to increase venous return, leading to enhanced SV, CO, and MAP, which are vital for combating circulatory failure and improving outcomes in pts with hypovolemic shock, could be pivotal for its resuscitative effects |
| 25 | Chalkias et al. [79], 2024 | Rat (27) and Rabbit (59) | Effect of centhaquine on the coagulation cascade using thromboelastography (Teg) | The study evaluated the effects of centhaquine on blood coagulation in both normal and uncontrolled hemorrhage conditions using ex vivo and in vivo experiments. In normal rat blood, centhaquine did not affect TEG parameters or alter the anticoagulant effects of ASA and heparin. In uncontrolled hemorrhage in New Zealand white rabbits, three resuscitation groups were studied: Sal-MAP 45, Centh-MAP 45 (centhaquine + saline), and Sal-MAP 60. Centhaquine increased MA significantly in the Centh-MAP 45 group vs. Sal-MAP 45, without altering other TEG parameters. The Sal-MAP 60 group showed changes indicating impaired coagulation | Overall, centhaquine did not impair coagulation and facilitated hemostatic resuscitation, suggesting its potential benefit in hemorrhage management |
| 26 | Gulati et al., 2025 | Human (45) | Subgroup analysis of hypovolemic shock patients with significant sepsis | Subgroup analyses of data from phase II (NCT04056065), phase III (NCT04045327), and phase IV (NCT05956418) clinical trials. Efficacy and safety of centhaquine citrate as a resuscitative agent for pts with hypovolemic shock and significant sepsis were assessed. Results demonstrated that centhaquine as an adjuvant to standard of care is safe, well-tolerated, and effective in pts with hypovolemic shock and significant sepsis. Pts treated with centhaquine showed statistically significant improvements in various shock-related endpoints, including reduced vasopressor requirements, better changes in SOFA scores, SBP and DBP, lactate levels, and base deficit than those receiving NS. The centhaquine group also exhibited significant improvements in SOFA score, a key prognostic indicator for sepsis, and required less vasopressor treatment. These findings suggest that centhaquine has the potential to be developed as a new resuscitative agent for septic shock | Centhaquine's beneficial effects in hypovolemic shock with sepsis can be attributed to the improved circulatory stability, reduced requirement for vasopressors, and improvements in SOFA scores |
AE adverse event, AKI acute kidney injury, AR adrenoceptor , ARDS acute respiratory distress syndrome, ASA acetylsalicylic acid (aspirin), Bmax binding density, BP blood pressure, bpm beats per minute, CO cardiac output, CV cardiovascular, DB double-blind, DBP diastolic blood pressure, DMPP dimethyl phenyl piperazinium iodide, ETA endothelin A, ETB endothelin B, h hour(s), HES hydroxyethyl starch, HIF hypoxia-inducible factor, HR heart rate, HS hypertonic saline, IC50 half-maximal inhibitory concentration, ICU intensive care unit, IQR interquartile range, IV intravenous, IVC inferior vena cava, KCl potassium chloride, Kcp intercompartmental transfer rate, Kd binding affinity, Ke elimination coefficient, Kpc reverse intercompartmental transfer rate, LPS lipopolysaccharide, LR lactated ringer’s, LVEF left ventricular ejection fraction, LVFS left ventricular fractional shortening, LVOT-VTI left ventricular outflow tract velocity-time integral, MA maximum amplitude, MAD multiple ascending dose, MAP mean arterial pressure, min minutes, mo months, MODS multiple organ dysfunction syndrome, MTD maximum tolerated dose, n number, NE norepinephrine, NGAL neutrophil gelatinase-associated lipocalin, NS normal saline, PC placebo-controlled, PHD-3 prolyl hydroxylase-3, PP pulse pressure, pts patient(s), SAD single ascending dose, SBP systolic blood pressure, SD Sprague–Dawley, SHR spontaneously hypertensive rats, SI Shock Index, SOFA Sequential Organ Failure Assessment, SV stroke volume, SVR systemic vascular resistance, SW stroke work, TEG thromboelastography, V volume of distribution, Vc central volume of distribution, Vp peripheral volume of distribution, WKY Wistar–Kyoto, 5-HT serotonin.