background

Hypovolemic Shock

icon

Centhaquine (Lyfaquin®) is a novel, first-in-class resuscitative agent for the treatment of hypovolemic shock.

It acts on α2B adrenergic receptors to produce venous constriction and increase venous return to the heart, resulting in an increase in cardiac output and improved tissue perfusion. Centhaquine also acts on central α2A adrenergic receptors to reduce sympathetic drive and decrease systemic vascular resistance contributing to an improved tissue blood perfusion. Mechanism of action of centhaquine makes it an ideal candidate for the treatment of patients with hypovolemic shock.

Enhancing tissue blood perfusion is a significant advantage in reducing the volume of resuscitation and preventing extravasation of fluid and adverse effect of lung edema. Centhaquine does not act on beta-adrenergic receptors, and therefore the risk of arrhythmias is mitigated.

Safety and efficacy of centhaquine was evaluated extensively in preclinical models, healthy volunteers and in patients. Centhaquine was found to be effective in multi-center, randomized, placebo-controlled phase II and III clinical studies with significant improvement in blood lactate levels, base deficit, blood pressure and mortality.

Centhaquine has been launched in India under the brand name Lyfaquin®.

background

Status of Hypovolemic Shock

Products Pre-Clinical Clinical Market
Phase 1 Phase 2 Phase 3
Hypovolemic Shock (Centhaquine - Lyfaquin®)
Publications
# Publication List
background Gulati A, Choudhuri R, Gupta A, Singh S, Ali SN, Sidhu GK, Haque PD, Rahate P, Bothra AR, Singh GP, Maheshwari S. A multicentric, randomized, controlled phase III study of centhaquine (Lyfaquin®) as a resuscitative agent in hypovolemic shock patients. medRxiv. 2020 Jan 1
background Gulati A, Lavhale M, Giri R, Andurkar S, Xanthos T, Gras J, Chopra S, Thakare R, Dasgupta A, Zafar MU, Badimon JJ. Centhaquine citrate. Alpha2B-Adrenoceptor ligand, Resuscitative agent for hypovolemic shock. Drugs Fut. 2020;45(3):153-63
background Gulati, A., D. Jain, N. R. Agrawal, S. Das, R. Chowdhuri, M. Prabhu, S. Haveri, R. Agarwal and M. S. Lavhale (2018). "Clinical Results Indicating Effectiveness of PMZ-2010 (Centhaquin) as a Novel Resuscitative Agent for Hypovolemic Shock." Circulation 138: A13092.
background Gulati, A., D. Jain, N. R. Agrawal, P. Rahate, S. Das, R. Chowdhuri, D. Dhibar, M. Prabhu, S. Haveri, R. Agarwal and M. S. Lavhale (2018). "Clinical Phase II Results of PMZ-2010 (Centhaquin) As A Resuscitative Agent for Hypovolemic Shock." Critical Care Medicine 147(1): 23.
background Gulati A, Jain D, Agrawal N, Rahate P, Das S, Chowdhuri R, Prabhu M, Haveri S, Dhibar D, Lavhale M. 1732: A PHASE II MULTICENTRIC RANDOMIZED CONTROLLED STUDY OF CENTHAQUINE IN HEMORRHAGIC SHOCK PATIENTS. Critical Care Medicine. 2020 Jan 1;48(1):840.
background Gulati A, Jain D, Agrawal N, Rahate P, Das S, Chowdhuri R, Dhibar D, Prabhu M, Haveri S, Agarwal R, Lavhale M. 23: CLINICAL PHASE II RESULTS OF PMZ-2010 (CENTHAQUIN) AS A RESUSCITATIVE AGENT FOR HYPOVOLEMIC SHOCK. Read Online: Critical Care Medicine| Society of Critical Care Medicine. 2019 Jan 1;47(1):12.
background Gulati A, Jain D, Agrawal NR, Das S, Chowdhuri R, Prabhu M, Haveri S, Agarwal R, Lavhale MS. Clinical Results Indicating Effectiveness of PMZ-2010 (Centhaquin) as a Novel Resuscitative Agent for Hypovolemic Shock. Circulation. 2018 Nov 6;138(Suppl_1):A13092-
background Gulati, A., Goyal, A. O., and Lavhale, M. S. (2016) Human Pharmacokinetics of Centhaquin Citrate, a Novel Resuscitative Agent. Circulation 134:A16607
background O'Donnell, J. N., O'Donnell, E. P., Kumar, E. J., Lavhale, M. S., Andurkar, S. V., Gulati, A., and Scheetz, M. H. (2016) Pharmacokinetics of centhaquin citrate in a dog model. J Pharm Pharmacol 68, 803-809
background O'Donnell, J. N., Gulati, A., Lavhale, M. S., Sharma, S. S., Patel, A. J., Rhodes, N. J., and Scheetz, M. H. (2016) Pharmacokinetics of centhaquin citrate in a rat model. J Pharm Pharmacol 68, 56-62
background Gulati, A., Zhang, Z., and Arshad, K. (2011) Centhaquin Decreases the Requirement of Norepinephrine, Maintains Blood Pressure and Improves Survival Following Resuscitation of Hemorrhaged Rats. Crit Care Med 39, 114
background Gulati, A., Pais, G., Mulloy, N., and Zhang, Z. (2013) Effect of Centhaquin Resuscitation on Coagulation in a Rabbit Model of Uncontrolled Hemorrhagic Shock. Clin Pharmacol in Drug Develop 1710539
background Pais, G., and Gulati, A. (2012) Effect of Centhaquin on the Coagulation cascade using Thromboelastography (TEG). Crit Care Med 40, 181
background Kontouli, Z., Staikou, C., Iacovidou, N., Mamais, I., Kouskouni, E., Papalois, A., Papapanagiotou, P., Gulati, A., Chalkias, A., and Xanthos, T. (2018) Resuscitation with centhaquin and 6% hydroxyethyl starch 130/0.4 improves survival in a swine model of hemorrhagic shock: a randomized experimental study. Eur J Trauma Emerg Surg
background Briyal, S., Gandhakwala, R., Khan, M., Lavhale, M. S., and Gulati, A. (2018) Alterations in endothelin receptors following hemorrhage and resuscitation by centhaquin. Physiol Res 67, S199-S214
background Papapanagiotou, P., Xanthos, T., Gulati, A., Chalkias, A., Papalois, A., Kontouli, Z., Alegakis, A., and Iacovidou, N. (2016) Centhaquin improves survival in a swine model of hemorrhagic shock. J Surg Res 200, 227-235
background Gulati A, Zhang Z, Arshad K. 414: CENTHAQUIN DECREASES THE REQUIREMENT OF NOREPINEPHRINE, MAINTAINS BLOOD PRESSURE AND IMPROVES SURVIVAL FOLLOWING RESUSCITATION OF HEMORRHAGED RATS. Critical Care Medicine. 2011 Dec 1;39(12):114.
background Leonard, M., Zhang, Z., Briyal, S., Pais, G., Patel, S., and Gulati, A. (2016) Centhaquin Citrate Improves Cerebral Blood Flow and Reduces Oxidative Stress Following Hemorrhagic Shock in Rats. Circulation 134:A16059
background Gulati, A. (2016) Vascular Endothelium and Hypovolemic Shock. Curr Vasc Pharmacol 14, 187-195
background Goyal, A. O., Lavhale, M. S., and Gulati, A. (2015) Safety and Efficacy of Centhaquin as a Novel Resuscitative Agent for Hypovolemic Shock. Circulation 132:A17521
background Reniguntala, M. S., Lavhale, M. S., Andurkar, S. V., and Gulati, A. (2015) Synthesis and characterization of centhaquin and its citrate salt and a comparative evaluation of their cardiovascular actions. Drug Res (Stuttg) 65, 184-191
background Gulati, A., and Lavhale, M. (2014) Repositioning of Centhaquin as a Novel Resuscitative Agent. Basic Clin Pharmacol 115, 43-43
background Lavhale, M. S., Havalad, S., and Gulati, A. (2013) Resuscitative effect of centhaquin after hemorrhagic shock in rats. J Surg Res 179, 115-124
background Gulati, A., Mulloy, N., Zhang, Z., and Pais, G. (2013) Resuscitative efficacy of centhaquin in a rabbit model of uncontrolled hemorrhagic shock. Crit Care Med 534
background Gulati, A., Zhang, Z., Murphy, A., and Lavhale, M. S. (2013) Efficacy of centhaquin as a small volume resuscitative agent in severely hemorrhaged rats. Am J Emerg Med 31, 1315-1321
background Lavhale, M. S., and Gulati, A. (2012) Effect of Centhaquin resuscitation on cardiovascular functions and plasma cytokines of hemorrhaged rats. Clin Pharmacol in Drug Develop 1, 215
background Lavhale, M. S., and Gulati, A. (2012) Centhaquin resuscitation improves survival of hemorrhaged rats. Indian J Pharmacol 44, S80
background Gulati, A., Voshtina, E., Zhang, Z., and Murphy, M. (2012) Alpha adrenergic receptors mediate resuscitative effect of Centhaquin in hemorrhaged rats. Crit Care Med 40(12), 587
background Gulati, A., Lavhale, M. S., Garcia, D. J., and Havalad, S. (2012) Centhaquin improves resuscitative effect of hypertonic saline in hemorrhaged rats. J Surg Res 178, 415-423
background Gulati, A. (2012) Pharmacology and toxicology of centhaquin: A resuscitative agent. The 32nd Annual Conference of Society of Toxicology (STOX), CSIR-Indian Institute of Toxicology Research, Lucknow.
background Briyal, S., Lavhale, M. S., and Gulati, A. (2012) Repeated administration of centhaquin to pregnant rats did not affect postnatal development and expression of endothelin receptors in the brain, heart or kidney of pups. Arzneimittelforschung 62, 670-676
background Tolentino, S., Havalad, S., Gulati, A., and Lavhale, M. (2011) Role of Centhaquin in the Resuscitation of Hemorrhagic Shock. Chest 140, 318A
background Gulati, A., Lavhale, M. S., and Havalad, S. (2011) Role of centhaquin in the resuscitation of hemorrhagic shock. J Clin Pharmacol 51, 1349-1349
background Gulati, A., Hussain, G., and Srimal, R. C. (1991) Effect of repeated administration of centhaquin, a centrally acting hypotensive drug, on adrenergic, cholinergic (muscarinic), dopaminergic, and serotonergic receptors in brain-regions of rat. Drug Develop Res 23, 307-323
background Srimal, R. C., Gulati, K., Nityanand, S., and Dhawan, B. N. (1990) Pharmacological studies on 2-(2-(4-(3-methylphenyl)-1-piperazinyl)ethyl) quinoline (centhaquin). I. Hypotensive activity. Pharmacol Res 22, 319-329