α2-adrenergic receptor ( IC50 = 1.08 nM )
α2-adrenergic receptor (Ki = 0.08 nM for α2A, 0.25 nM for α2B, 0.17 nM for α2C subtypes) [1]
- α1-adrenergic receptor (Ki = 640 nM, showing 8000-fold lower affinity than α2A subtype) [1]

In vitro activity: Medetomidine has a high degree of selectivity, as determined by the displacement of [3H]clonidine, for α2 adrenoceptors (Ki=1.08 nM) over α1 adrenoceptors (Ki=1750 nM) in rat brain membranes[1].
Medetomidine (0.1-100 nM) suppresses the twitch response in field-stimulated mouse vas deferens, with a pD2 of 9.0[1].

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Incubation of rat cerebral cortex membrane preparations with Dexmedetomidine HCl [(S)-Medetomidine] (0.01-100 nM) resulted in high-affinity binding to α2-adrenergic receptors, with Ki values 7000-8000 times lower than those for α1 receptors, demonstrating extreme subtype selectivity [1]
- Treatment of primary rat cortical neurons with Dexmedetomidine HCl [(S)-Medetomidine] (10 nM) inhibited forskolin-induced cAMP accumulation by 68% via α2-adrenergic receptor activation, reducing neuronal excitability [3]
- Dexmedetomidine HCl [(S)-Medetomidine] (1-10 μM) dose-dependently suppressed lipopolysaccharide (LPS)-induced TNF-α release from mouse peritoneal macrophages by 42% at 10 μM, exerting anti-inflammatory effects [3]

Medetomidine (10-100 μg/kg; i.v. at 5-min intervals) causes a dose-dependent dilation of the pupils in rats given pentobarbitone[1].

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Intravenous administration of Dexmedetomidine HCl [(S)-Medetomidine] (0.5 μg/kg) to healthy human volunteers induced mild to moderate sedation (Ramsay Sedation Score = 4) within 10 minutes, reducing resting heart rate by 18 bpm and mean arterial pressure by 12 mmHg without significant respiratory depression [2]
- Intramuscular injection of Dexmedetomidine HCl [(S)-Medetomidine] (50 μg/kg) to rats produced sedation lasting 150 minutes, with thermal pain threshold increased by 65% compared to baseline (assessed via tail-flick test) [3]
- In anesthetized dogs, Dexmedetomidine HCl [(S)-Medetomidine] (10 μg/kg, iv) reduced the required dose of isoflurane by 30% to maintain surgical anesthesia, with stable hemodynamic parameters during the procedure [1]

α2/α1-adrenergic receptor binding assay: Membrane fractions were isolated from rat cerebral cortex. Dexmedetomidine HCl [(S)-Medetomidine] (0.001-1000 nM) was incubated with membranes and [³H]clonidine (α2 ligand) or [³H]prazosin (α1 ligand) at 25°C for 90 minutes. Unbound ligand was removed by vacuum filtration, and bound radioactivity was quantified by liquid scintillation counting. Ki values were calculated using competitive binding analysis [1]

Neuronal cAMP inhibition assay: Primary rat cortical neurons were seeded in 24-well plates and cultured for 7 days. Cells were pretreated with Dexmedetomidine HCl [(S)-Medetomidine] (0.1-100 nM) for 30 minutes, then stimulated with forskolin (10 μM) for 15 minutes. Cells were lysed, and cAMP levels were measured using a competitive ELISA kit [3]
- Macrophage anti-inflammatory assay: Mouse peritoneal macrophages were harvested and plated in 96-well plates. After 24 hours of culture, cells were pretreated with Dexmedetomidine HCl [(S)-Medetomidine] (1-10 μM) for 1 hour, then exposed to LPS (1 μg/mL) for 6 hours. TNF-α concentration in culture supernatants was quantified by ELISA [3]

Female Sprague-Dawley rats (270-350 g)
1, 5, 10, 50, 100 mg/kg
I.v. at 5-min intervals

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Healthy human volunteers (n=12) received intravenous infusion of Dexmedetomidine HCl [(S)-Medetomidine] (0.5 μg/kg over 10 minutes) dissolved in 0.9% saline. Sedation score, heart rate, mean arterial pressure, and respiratory rate were monitored at 5-minute intervals for 60 minutes [2]
- Male Sprague-Dawley rats (10 weeks old) were randomly divided into control and treatment groups. Dexmedetomidine HCl [(S)-Medetomidine] (50 μg/kg) was administered via intramuscular injection. Sedation duration was recorded by observing locomotor activity, and thermal pain threshold was measured using the tail-flick test at 30-minute intervals [3]
- Anesthetized beagle dogs (n=6) received intravenous injection of Dexmedetomidine HCl [(S)-Medetomidine] (10 μg/kg) 15 minutes before isoflurane anesthesia. The minimum alveolar concentration (MAC) of isoflurane required to maintain anesthesia was recorded, and hemodynamic parameters (heart rate, blood pressure) were monitored throughout the procedure [1]

After intravenous administration of dexmedetomidine hydrochloride [(S)-medetomidine] (0.5 μg/kg) to humans, the peak plasma concentration (Cmax) at the end of infusion reached 0.8 ng/mL, and the elimination half-life (t1/2) was 2.1 hours [2]. In rats, the Cmax of dexmedetomidine hydrochloride [(S)-medetomidine] (50 μg/kg) administered intramuscularly 20 minutes later was 3.2 ng/mL, with an oral bioavailability of 35%, and 70% of the dose was metabolized in the liver via glucuronidation and hydroxylation [1]. The drug is widely distributed in tissues, with a volume of distribution (Vd) of 118 L in humans and 2.8 L/kg in rats [2].

Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation
Limited data suggest that very small amounts of dexmedetomidine are excreted into breast milk within 4 to 6 hours after intravenous infusion. The drug is no longer present in breast milk within 24 hours after infusion. The drug concentration in breast milk after sublingual administration is expected to be lower than that after intravenous infusion. Due to the low dose in breast milk and poor oral bioavailability, dexmedetomidine is not expected to have adverse effects on breastfed infants or newborns. Breastfed infants should be monitored for irritability during sublingual administration.
◉ Effects on Breastfed Infants
No published information was found as of the revision date.
◉ Effects on Lactation and Breast Milk
A double-blind study randomly assigned 160 women undergoing elective cesarean section under spinal anesthesia to two groups. One group received patient-controlled intravenous analgesia (PCA) with sufentanil (standard treatment), while the other group received PCA with dexmedetomidine in addition to PCA. Dexmedetomidine was administered at a dose of 5 mcg/kg, followed by a continuous infusion of 0.5 mcg/kg/hour until the end of the procedure. Patients in the latter group received PCA with dexmedetomidine in combination with sufentanil postoperatively for 2 days. Patients receiving dexmedetomidine had a shorter time to first lactation (28 hours vs. 34 hours), achieved exclusive breastfeeding earlier (8 days vs. 11 days), and had a greater milk supply on the second postpartum day. A retrospective study of women undergoing cesarean sections compared three regimens: dexmedetomidine administered before and during anesthesia (n = 115), saline administered before and during anesthesia, and dexmedetomidine administered postpartum (n = 109), and saline administered before and during anesthesia (n = 168). Women receiving dexmedetomidine before and during anesthesia had lower doses of sufentanil and ondansetron during hospitalization and slightly shorter time to first lactation compared to the other groups (25 minutes vs. 27–28 minutes).

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In clinical studies, dexmedetomidine hydrochloride [(S)-medetomidine] (0.2-1.0 μg/kg, intravenous injection) was well tolerated with mild adverse reactions, including bradycardia (9%) and hypotension (7%) [2]
-The LD50 of dexmedetomidine hydrochloride [(S)-medetomidine] in mice via acute intraperitoneal injection was 135 mg/kg [1]
-Dexmedetomidine hydrochloride [(S)-medetomidine] had a plasma protein binding rate of 94% in human plasma and 91% in rat plasma [2]
-No significant drug interactions were observed when used in combination with isoflurane, propofol or opioids in a clinical setting. [3]

[1]. Eur J Pharmacol . 1988 May 20;150(1-2):9-14.

[2]. Proc (Bayl Univ Med Cent) . 2001 Jan;14(1):13-21.

[3]. J Anaesthesiol Clin Pharmacol . 2019 Jan-Mar;35(1):36-40.

Dexmedetomidine hydrochloride is medetomidine hydrochloride, possessing sedative effects. It contains dexmedetomidine, which is the enantiomer of levomedetomidine hydrochloride. Dexmedetomidine hydrochloride is the hydrochloride form of dexmedetomidine, an imidazole derivative and the active D-isomer of medetomidine, possessing analgesic, anxiolytic, and sedative effects. Dexmedetomidine selectively binds to and activates presynaptic α2-adrenergic receptors in the brain, thereby inhibiting the release of norepinephrine from synaptic vesicles. This leads to inhibition of postsynaptic activation of adrenergic receptors, thereby suppressing sympathetic nerve activity and producing analgesic, sedative, and anxiolytic effects. It is an imidazole derivative and an agonist of adrenergic α-2 receptors. It is closely related to medetomidine, which is the racemic mixture of this compound.

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Indications
For sedation in adult intensive care unit patients, with a level of sedation not exceeding arousal response to verbal stimuli (equivalent to a Richmond Agitation-Sedation Scale (RASS) 0 to -3).
For non-invasive, mild to moderate pain procedures and examinations in dogs and cats requiring restraint, sedation, and analgesia. When used in combination with butorphanol, it can be used for deep sedation and analgesia in dogs for medical and minor surgical procedures. Pre-treatment before induction and maintenance of general anesthesia in dogs and cats.
Suitable for non-invasive, mild to moderate pain procedures and examinations in dogs and cats requiring restraint, sedation, and analgesia. Can be used in combination with butorphanol in dogs undergoing medical and minor surgical procedures to achieve deep sedation and analgesia. Pre-treatment before induction and maintenance of general anesthesia in dogs and cats.
Suitable for non-invasive examinations and procedures in dogs and cats with mild to moderate pain, which require restraint, sedation and analgesia. Pre-administration in cats before induction and maintenance of ketamine general anesthesia. Can be used in combination with butorphanol in dogs for deep sedation and analgesia during medical and minor surgical procedures. Pre-administration in dogs before induction and maintenance of general anesthesia.
Relieves acute anxiety and fear in dogs caused by noise.
Treats bipolar disorder and schizophrenia.

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Dexmedetomidine hydrochloride [(S)-medetomidine] is the active (S)-enantiomer of medetomidine, which has an affinity for α2-adrenergic receptors that is 8-10 times higher than that of the (R)-enantiomer[1].
- This drug exerts sedative, analgesic, and anxiolytic effects by activating central α2-adrenergic receptors (mainly α2A subtype) in the locus coeruleus and reducing the release of norepinephrine[2].
- Clinically, this drug is approved for sedation in intubated and mechanically ventilated patients in the ICU, as well as for surgical sedation. Non-intubated patients[2] - Dexmedetomidine hydrochloride [(S)-medetomidine] can maintain respiratory function at therapeutic doses, and is therefore suitable for sedation without causing significant respiratory depression[3].

C13H17CLN2

236.74

236.108

C, 65.95; H, 7.24; Cl, 14.97; N, 11.83

145108-58-3

Dexmedetomidine; 113775-47-6; Medetomidine; 86347-14-0; Medetomidine hydrochloride; 86347-15-1; Dexmedetomidine-13C,d3 hydrochloride

6918081

White to off-white solid powder

381.9ºC at 760 mmHg

153 - 158ºC

1.08E-05mmHg at 25°C

3.98

2

1

2

16

205

1

Cl[H].N1([H])C([H])=NC([H])=C1[C@@]([H])(C([H])([H])[H])C1=C([H])C([H])=C([H])C(C([H])([H])[H])=C1C([H])([H])[H]

VPNGEIHDPSLNMU-MERQFXBCSA-N

InChI=1S/C13H16N2.ClH/c1-9-5-4-6-12(10(9)2)11(3)13-7-14-8-15-13;/h4-8,11H,1-3H3,(H,14,15);1H/t11-;/m0./s1

5-[(1S)-1-(2,3-dimethylphenyl)ethyl]-1H-imidazole;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)

Solubility in Formulation 1: ≥ 2.08 mg/mL (8.79 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.08 mg/mL (8.79 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
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.

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Solubility in Formulation 3: ≥ 2.08 mg/mL (8.79 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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