Function of ICI 174,864 in traumatic hemorrhagic shock

2018-08-18

Introduction 

ICI 174,864 is an opioid peptide, belonging to subclasses of opioid receptors. Its chemical structure is N, N-diallyl-Tyr-Aib-Aib-Phe-Leu. It has significant effects in various kinds of circulatory shock. The opioid receptor antagonists are positive to circulatory shock. δ and κ opioid receptors have been proved as the main receptors participating in traumatic shock. ICI 174,864, as one of δ opioid receptor antagonists, is beneficial for traumatic shock.

Pharmacologic action

δ opioid receptor antagonist has inotropic and vasoconstriction effects. ICI 174,864is considered to be suitable for the early treatment of traumatic hemorrhagic shock. This antishock effect is somewhat dependent on fluid resuscitation and plays a positive role in the subsequent treatment of traumatic shock. ICI 174,864 directly affects peripheral δ opioid receptors in cardiovascular system or activates the sympathetic system by central or peripheral system. ICI 174,864 increased the mean arterial pressure after hemorrhagic shock in rats. Comparing with the control group, ICI 174,864 markedly prolongs survival time. Early administration of ICI 174, 864 can buy time for subsequent treatment of traumatic and hemorrhagic shock.

Function

Endogenous opioid peptides are neuroendocrine mediators released from the pituitary gland, which are closely related to shock. Among these peptides, δ opioid receptor is the main receptor in hemorrhagic shock, which is involved in protective behavior of heart after ischemic preconditioning by activating the ATP-sensitive potassium channel and protein kinase. The δ opioid receptor antagonist ICI 174,864 has been proved to be beneficial for the treatment of rats at the beginning stage of traumatic hemorrhagic shock. The treatment by ICI 174,864 can essentially improve hemodynamic parameters, tissue bleeding, cardiac function and so on in hemorrhagic shock rats. ICI 174,864 shows its anti-shock feature by enhancing hemodynamics, cardiac function, and tissue bleeding.

Pharmacokinetics and metabolism

The δ opioid receptor antagonist ICI 174,864 is beneficial for traumatic shock. It provides anti-shock ability at early stage of hemorrhagic shock to buy time for the subsequent treatment. ICI 174,864 increased the mean arterial pressure with the dosage after hemorrhagic shock in rats. The mean arterial pressure of the experimental rats treated with 3 mg/kg of ICI 174,864 with lactated Ringer's solution infusion of 0 and 1/4 volume can be maintained at about 60mmHg for 3h, 70mmHg for 3h, respectively. And the mean arterial pressure increases to 50 mmHg after ICI 174,864 administration, yet rapidly decreases to less than 40mmHg at 2h. ICI 174,864 markedly increases blood flow in liver and kidney.

References

1. Liu L, Tian K, Zhu Y, Ding X, Li T. δ opioid receptor antagonist, ICI 174,864, is suitable for the early treatment of uncontrolled hemorrhagic shock in rats. Anesthesiology, 2013, 119, 379-388.

2. Liu L, Hu D, Pan X, Lu R, Dan F. Subclass opioid receptors associated with the cardiovascular depression after traumatic shock and the antishock effects of its specific receptor antagonists. Shock, 2005, 24, 470-475.

3. Glattard E, Welters ID, Lavaux T, Muller AH, Laux A, Zhang D, Schmit AR, Delalande F, Laventie BJ, Dirrig-Grosch S, Colin DA, Van Dorsselaer A, Aunis D, Metz-Boutigue MH, Schneider F, Goumon Y. Endogenous morphine levels are increased in sepsis: a partial implication of neutrophils. PLoS One, 2010, 5, e8791.

4. Schultz JE, Hsu AK, Gross GJ. Ischemic preconditioning in the intact rat heart is mediated by delta 1- but not mu- or kappa-opioid receptors. Circulation, 1998, 97, 1282-1289.

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