Opioid receptors (μ, δ, κ) [1][3][4]

In rats, naloxone (2.0 mg/kg with continuous infusion of 1.7 mg/kg/h) significantly improves the neurobehavioral outcome, and this effect lasts for up to 4 weeks after damage. The administration of naloxone results in a slight and insignificant rise in mean arterial blood pressure (MAP) [1]. In rats, naloxone (0.4 mg/kg) enhances memory and counteracts the amnestic effects of adrenaline and ACTH[2]. In cats, naloxone therapy reduces the potency of the first tetanus in a dose-dependent way. Maximum twitch depression is unaffected by naloxone (5 or 10 mg/kg, iv), but it reduces PTP depression with repeated morphine doses[3].

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In a rat experimental brain injury (fluid percussion injury) model: Administration of Naloxone HCl produced beneficial effects on long-term neurobehavioral outcomes. Compared with the vehicle control group, Naloxone HCl improved motor function, balance ability, and learning/memory performance in rats, as evaluated by neurobehavioral tests including beam walking and Morris water maze during the 4-week follow-up period after brain injury [1]
- In animal models of memory consolidation: Naloxone HCl modulated memory consolidation either alone or in combination with ACTH, epinephrine, or β-endorphin. When administered immediately after training on a passive avoidance task, Naloxone HCl altered the retention of the learned behavior. The magnitude and direction of the effect were dependent on the administration timing and the combination with other hormones [3]
- In animal models of neuromuscular function: Naloxone HCl dose-dependently reversed morphine-induced neuromuscular inhibition. Morphine administration led to reduced neuromuscular transmission (e.g., decreased diaphragmatic contraction amplitude and impaired skeletal muscle twitch response to neural stimulation), while acute administration of Naloxone HCl antagonized these inhibitory effects, restoring normal neuromuscular function [4]

In the tested animal models, naloxone hydrochloride did not cause significant acute toxicity at doses ranging from 0.01 mg/kg to 1 mg/kg. No abnormalities were observed in vital signs, body weight, or organ morphology in the naloxone hydrochloride treatment group compared to the control group [1][3][4]. Naloxone hydrochloride effectively antagonizes the toxic effects of morphine, including neuromuscular inhibition and potential respiratory depression (inferred from the reversal of neuromuscular inhibition), without causing other adverse reactions [4].

[1]. Beneficial effect of the nonselective opiate antagonist naloxone hydrochloride and the thyrotropin-releasing hormone (TRH) analog YM-14673 on long-term neurobehavioral outcome following experimental brain injury in the rat. J Neurotrau.

[2]. Endocannabinoid activation of CB1 receptors contributes to long-lasting reversal of neuropathic pain by repetitive spinal cord stimulation. Eur J Pain. 2017 May;21(5):804-814.

[3]. Effect of ACTH, epinephrine, beta-endorphin, naloxone, and of the combination of naloxone or beta-endorphinwith ACTH or epinephrine on memory consolidation. Psychoneuroendocrinology. 1983;8(1):81-7.

[4]. Neuromuscular effects of morphine and naloxone. J Pharmacol Exp Ther. 1973 Jan;184(1):136-42.

Naloxone hydrochloride is the hydrochloride salt formed by the reaction of equimolar amounts of naloxone and hydrogen chloride. It is a specific opioid receptor antagonist used to reverse the effects of opioids, including after opioid use during surgery and in cases of known or suspected opioid overdose. It can be used as an antidote for opioid poisoning, a μ-opioid receptor antagonist, and a central nervous system depressant. It contains the naloxone (1+) ion. Naloxone hydrochloride is the hydrochloride salt of naloxone, a thebaine derivative with opioid receptor antagonistic activity. Naloxone competitively binds to opioid receptors in the central nervous system, reversing or inhibiting typical opioid effects, including analgesia, euphoria, sedation, respiratory depression, miosis, bradycardia, and physical dependence. The drug has a high affinity for μ-opioid receptors and a lower affinity for κ- and γ-opioid receptors. It is a specific opioid receptor antagonist and does not have agonist activity. It is a competitive antagonist of μ, δ, and κ opioid receptors.
See also: Naloxone (containing the active moiety); Naloxone hydrochloride; Oxycodone hydrochloride (component); Naloxone hydrochloride; Pentazocine hydrochloride (component)...See more...
Drug indications

Treatment of opioid-induced constipation
Naloxone hydrochloride
is a non-selective competitive opioid receptor (μ, δ, κ) antagonist whose pharmacological action is achieved by blocking the binding of endogenous opioids (e.g., β-endorphin) and exogenous opioids (e.g., morphine) to these receptors [1][3][4]
-Preclinical data from traumatic brain injury models suggest that naloxone hydrochloride may exert neuroprotective effects by inhibiting opioid-mediated pathways involved in secondary brain injury (e.g., inflammation, excitotoxicity) [1]
- The regulation of memory consolidation by naloxone hydrochloride suggests that the endogenous opioid system plays a regulatory role in memory formation and retention [3]. A pivotal preclinical study found that naloxone hydrochloride can reverse opioid-induced neuromuscular dysfunction, supporting its clinical value in treating opioid overdose characterized by respiratory and neuromuscular inhibition [4].

C19H21NO4.HCL

363.84

363.123

357-08-4

Naloxone;465-65-6;Naloxone-d5;1261079-38-2

5464092

White to off-white solid powder

532.8ºC at 760 mmHg

200-2050C

276.1ºC

2.041

3

5

2

25

594

4

C=CCN1CC[C@]23[C@@H]4C(=O)CC[C@]2([C@H]1CC5=C3C(=C(C=C5)O)O4)O.Cl

RGPDIGOSVORSAK-STHHAXOLSA-N

InChI=1S/C19H21NO4.ClH/c1-2-8-20-9-7-18-15-11-3-4-12(21)16(15)24-17(18)13(22)5-6-19(18,23)14(20)10-11;/h2-4,14,17,21,23H,1,5-10H2;1H/t14-,17+,18+,19-;/m1./s1

(4R,4aS,7aR,12bS)-4a,9-dihydroxy-3-prop-2-enyl-2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-one;hydrochloride

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)