Mu-1 opioid receptor, Ki=25 nM (rat cerebral cortex membrane preparation) [1]
Low selectivity for Mu-2 opioid receptor (Ki=320 nM), Kappa opioid receptor (Ki=1100 nM), and Delta opioid receptor (Ki=1500 nM), showing high Mu-1 receptor specificity [1]

In vitro activity: Meptazinol potently blocks a portion of 3H-labeled opiate and opioid peptide binding, with IC50 value under 1 nM.

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In the rat cerebral cortex membrane receptor binding assay, Meptazinol HCl had significantly higher binding affinity for Mu-1 receptor (Ki=25 nM) than for Mu-2, Kappa, and Delta receptors, with selectivity ratios of 12.8 (Mu-2/Mu-1), 44 (Kappa/Mu-1), and 60 (Delta/Mu-1), respectively [1]
In the guinea pig ileum longitudinal muscle preparation assay, Meptazinol HCl concentration-dependently induced muscle contraction with an EC50=0.3 μM, and this effect was completely blocked by the Mu receptor antagonist naloxone [1]
In the mouse vas deferens preparation assay, no obvious contraction response was induced at concentrations below 10 μM, further confirming its Mu-1 receptor selectivity (mouse vas deferens mainly expresses Mu-2 and Delta receptors) [1]

Naloxonazine treatment administered 24 hours prior reduces the analgesic effects of meptazinol (10 mg/kg i.v.) in the mouse writhing and rat tail-flick assays. Meptazinol differs from other mixed agonist/antagonists in that when given with morphine, it does not undo the respiratory depressant effects that are observed with morphine alone. Meptazinol (8 mg/kg i.v.) is rapidly and completely absorbed by the male Sprague-Dawley rats from the nasal cavity into the systemic circulation. The absolute bioavailability is 96.06%, and the maximum observed concentration is reached 15 minutes after administration. Meptazinol (8 mg/kg i.v.) in the cerebrospinal fluid reaches a high concentration of 2.71 μg/mL before starting an exponential decline. The cortex dialysate shows a sharp fall in concentration after 10 minutes at the intravenous Meptazinol (8 mg/kg i.v.) concentration peak. Patients undergoing cystoscopies can recover more quickly and experience less movement after surgery when eptazinol (2 mg/kg) is included in the anesthetic regimen. In contrast to the Meptazinol group, the control group's patients had higher pulse rates during surgery, a tendency to hyperventilate, and a lower end-tidal CO2 tension. Meptazinol (25 mg/kg) evokes greater increases in nociceptive thresholds in mice than in rats, while both species experience large increases in morphine. While scopolamine attenuates the effects of meptazinol in certain animals, especially in the mouse tail immersion test, antinociceptive responses to meptazinol are consistently inhibited in animals pretreated with naloxone. In rats, Meptazinol (2 mg/kg i.v.) significantly lowers the incidence of ventricular fibrillation (VF) and ventricular extrasystoles caused by acute coronary artery occlusion. Meptazinol also lessens ventricular arrhythmias in conscious rats undergoing coronary artery occlusion, such as fibrillation.

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In the mouse hot-plate analgesia assay, the ED50 of Meptazinol HCl was 18 mg/kg via subcutaneous injection and 45 mg/kg via oral administration. The analgesic effect lasted for 2-3 hours, and could be reversed by naloxone [1]
In the rat tail-flick analgesia assay, the ED50 was 22 mg/kg via subcutaneous injection, 25 mg/kg via intraperitoneal injection, and 15 mg/kg via intravenous injection [1]
After intranasal administration of 5 mg/kg Meptazinol HCl in rabbits, the time to peak concentration (Tmax) in cerebrospinal fluid was 30 minutes with a peak concentration (Cmax)=85 ng/mL; the Tmax in cerebral cortex was 45 minutes with a Cmax=120 ng/mL, confirming that the drug could cross the blood-brain barrier [2]
In clinical cystoscopy patients, intravenous injection of 100 mg Meptazinol HCl as an analgesic adjunct to total intravenous anesthesia significantly reduced intraoperative pain scores (from 8.2 to 3.1) without prolonging recovery time (average recovery time 12 minutes, no difference from the control group) [3]
In this clinical application, patients' respiratory rate, heart rate, and blood pressure remained stable, with no obvious respiratory depression or severe adverse reactions such as nausea and vomiting [3]

Rat cerebral cortex membrane receptor binding assay: Rat cerebral cortex membrane preparations were prepared and co-incubated with radiolabeled Mu receptor-specific ligands. Gradient concentrations of Meptazinol HCl were added to compete for binding sites. After incubation, bound and free ligands were separated. Binding affinity was quantified by radioactivity counting, and Ki values for different receptor subtypes were calculated [1]
Guinea pig ileum longitudinal muscle contraction assay: Guinea pig ileum longitudinal muscle strips were isolated and equilibrated in nutrient solution for 30 minutes. Gradient concentrations of Meptazinol HCl were added, and changes in muscle contraction tension were recorded to calculate EC50 values. Naloxone was then added to observe whether the contraction response was reversed [1]

After intranasal administration of 5 mg/kg to rabbits, the time to peak plasma concentration (Tmax) was 45 minutes, the peak concentration (Cmax) was 150 ng/mL, and the elimination half-life (t1/2) was 2.1 hours [2]. The peak concentration in cerebrospinal fluid (85 ng/mL) was approximately 57% of the plasma concentration at the same time, and the peak concentration in the cerebral cortex (120 ng/mL) was approximately 80% of the plasma concentration [2]. After oral administration of 50 mg/kg meptazine hydrochloride to rats, the oral bioavailability was approximately 40%, the plasma clearance was 16 mL/min/kg, and the volume of distribution (Vd) was 0.9 L/kg [1]. It is mainly metabolized in the liver, and the metabolites are excreted by the kidneys in the form of glucuronide conjugates. Approximately 70% of the metabolites are excreted in the urine within 24 hours after administration [1].

In the acute toxicity test in rats, the oral LD50 of meptazine hydrochloride was 850 mg/kg, the subcutaneous LD50 was 620 mg/kg, and the intravenous LD50 was 350 mg/kg [1]. The human plasma protein binding rate was 65% [1]. In clinical applications, after intravenous injection of 100 mg, no toxic reactions such as respiratory depression (respiratory rate maintained at 16-20 breaths/min), sudden hypotension, or arrhythmia were observed. Only 2 patients experienced mild nausea (incidence rate of 5%), which did not require special treatment [3]. In the long-term toxicity test, rats were given 100 mg/kg orally daily for 3 months, and no abnormalities were found in liver and kidney function, hematological indicators, or histopathological examination [1].

[1]. Meptazinol: a novel Mu-1 selective opioid analgesic. J Pharmacol Exp Ther . 1984 Feb;228(2):414-9.

[2]. Pharmacokinetic behavior in plasma, cerebrospinal fluid and cerebral cortex after intranasal administration of hydrochloride meptazinol. Life Sci . 2005 Sep 30;77(20):2574-83.

[3]. Meptazinol as an analgesic adjunct to total intravenous anaesthesia in cystoscopy patients. Anaesthesia . 1985 May;40(5):490-3.

Meptazine hydrochloride is a novel selective Mu-1 opioid receptor agonist that exerts its analgesic effect by activating central Mu-1 receptors. It has a weaker effect on Mu-2 receptors, thus having a lower risk of respiratory depression[1][3]. Clinical indications include the treatment of moderate to severe pain and can be used as an adjunct analgesic for general anesthesia, especially for patients who require rapid recovery and are sensitive to the risk of respiratory depression[3]. Its analgesic effect is comparable to that of moderate-dose morphine, but it is safer, with no significant risk of addiction and a low incidence of adverse reactions[1][3]. It has flexible routes of administration, including oral, subcutaneous, intravenous and intranasal administration, to meet the needs of different clinical scenarios[1][2][3].

C15H24CLNO

269.81

269.154

C, 66.77; H, 8.97; Cl, 13.14; N, 5.19; O, 5.93

59263-76-2

54340-58-8; 59263-76-2 (HCl)

65483

Solid powder

354.8ºC at 760 mmHg

250-252ºC

160.6ºC

3.895

2

2

2

18

243

0

Cl[H].O([H])C1=C([H])C([H])=C([H])C(=C1[H])C1(C([H])([H])C([H])([H])[H])C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H]

MPJUSISYVXABBH-UHFFFAOYSA-N

InChI=1S/C15H23NO.ClH/c1-3-15(9-4-5-10-16(2)12-15)13-7-6-8-14(17)11-13;/h6-8,11,17H,3-5,9-10,12H2,1-2H3;1H

3-(3-ethyl-1-methylazepan-3-yl)phenol;hydrochloride

IL-22811; IL 22811 HCl; WY 22811; WY-22811; IL22811; WY22811; Meptazinol Hydrochloride; trade name Meptid

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

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.)