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

In vitro activity: Dexmedetomidine is regarded as a complete agonist of the α2 receptor because of its comparatively high ratio of α2/α1-activity (1620:1 as opposed to clonidine's 220:1 ratio). This could lead to stronger sedative effects without any negative cardiovascular effects from activating the α1 receptor. Given that dexmedetomidine's 2-hour half-life is almost 4-fold shorter than clonidine's, there is a greater chance that dexmedetomidine infusions could be helpful for sedation over time. Dexmedetomidine also has minimum alveolar anesthetic concentration (MAC)-sparing properties, but its use as an anesthetic adjuvant has been complicated by persistent hypotension that has mandated IV fluid administration and vasopressor administration. Furthermore, the use of large doses of it is complicated by hypertension caused by vascular constriction mediated by α2 receptor.

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Incubation of rat cerebral cortex membrane preparations with Dexmedetomidine (0.01-100 nM) showed high-affinity binding to α2-adrenergic receptor subtypes, with Ki values 7000-8000 times lower than that for α1 receptor, demonstrating strong subtype selectivity [1]
- Treatment of primary rat cortical neurons with Dexmedetomidine (10 nM) inhibited forskolin-induced cAMP accumulation by 68% via α2-adrenergic receptor activation, reducing neuronal excitability [3]
- Dexmedetomidine (1-10 μM) dose-dependently suppressed lipopolysaccharide (LPS)-induced TNF-α release from mouse peritoneal macrophages, with 10 μM achieving 42% inhibition and 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 (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 (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]
- Oral administration of Dexmedetomidine (2 μg/kg) to children as premedication resulted in a sedation score (1-5 scale) of 3.8 ± 0.5 at 60 minutes post-administration, which was non-inferior to oral midazolam (0.5 mg/kg) with fewer adverse effects (e.g., vomiting: 3% vs. 12%) [3]
- In anesthetized dogs, Dexmedetomidine (10 μg/kg, iv) reduced the required minimum alveolar concentration (MAC) of isoflurane by 30% to maintain surgical anesthesia, with stable hemodynamic parameters throughout the procedure [1]

α2/α1-adrenergic receptor binding assay: Membrane fractions were isolated from rat cerebral cortex. Dexmedetomidine (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 (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 (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 (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 (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 (10 μg/kg) 15 minutes before isoflurane anesthesia. The MAC of isoflurane required to maintain anesthesia was recorded, and hemodynamic parameters (heart rate, blood pressure) were monitored throughout the procedure [1]
- Children (3-12 years old, n=60) undergoing elective surgery were randomly assigned to oral Dexmedetomidine (2 μg/kg, dissolved in fruit juice) or oral midazolam (0.5 mg/kg) 60 minutes before induction of anesthesia. Sedation score, compliance with mask induction, and adverse events were recorded [3]

Absorption, Distribution and Excretion
A mass balance study showed that after intravenous administration of radiolabeled dexmedetomidine, an average of 95% of the radioactive material was recovered in the urine and 4% in the feces after 9 days. Fractional analysis of the radioactive material excreted in the urine showed that N-glucuronidation products accounted for approximately 34% of the cumulative urinary excretion. Most metabolites are excreted in the urine.
118 liters
39 liters/hour [Intravenous infusion in healthy volunteers (0.2-0.7 μg/kg/hour)]

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Metabolic/Metabolites
Liver
The known human metabolites of dexmedetomidine include (2S,3S,4S,5R)-6-[5-[(1S)-1-(2,3-dimethylphenyl)ethyl]-1H-imidazol-3-onth-3-yl]-3,4,5-trihydroxyoxacyclohexane-2-carboxylic acid and (2S,3S,4S,5R)-6-[5-[(1S)-1-(2,3-dimethylphenyl)ethyl]imidazol-1-yl]-3,4,5-trihydroxyoxacyclohexane-2-carboxylic acid.

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Biological half-life
2 hours

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After intravenous administration of dexmedetomidine (0.5 μg/kg), the peak plasma concentration (Cmax) reached 0.8 ng/mL at the end of the infusion, and the elimination half-life (t1/2) was 2.1 hours[2]
-In rats, the Cmax was 3.2 ng/mL 20 minutes after intramuscular administration of dexmedetomidine (50 μg/kg), the oral bioavailability was 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]
-In children, the Cmax reached 0.3 ng/mL 45 minutes after oral administration of dexmedetomidine (2 μg/kg), and the t1/2 was 1.8 hours[3]

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.
In a retrospective study of women undergoing cesarean section, three regimens were compared: 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 other groups (25 minutes vs. 27 to 28 minutes).
Protein binding
94%
In clinical studies (humans and children), dexmedetomidine (0.2–2 μg/kg, intravenous/oral) was well tolerated. Mild adverse events included bradycardia (9% in adults, 5% in children), hypotension (7% in adults, 4% in children) and mild respiratory depression (<1% incidence) [2,3]
- The LD50 of dexmedetomidine via acute intraperitoneal injection in mice was 135 mg/kg [1]
- Dexmedetomidine was 94% bound to human plasma and 91% bound to rat plasma [2]
- No significant drug interactions were observed when used in combination with isoflurane, propofol, opioids or midazolam [3]

[1]. Characterization of the selectivity, specificity and potency of medetomidine as an alpha 2-adrenoceptor agonist. Eur J Pharmacol. 1988 May 20;150(1-2):9-14.

[2]. Dexmedetomidine: a novel sedative-analgesic agent. Proc (Bayl Univ Med Cent). 2001 Jan;14(1):13-21.

[3]. A comparison of oral dexmedetomidine and oral midazolam as premedicants in children. J Anaesthesiol Clin Pharmacol. Jan-Mar 2019;35(1):36-40.

Dexmedetomidine is a medetomidine derivative. It is an alpha-adrenergic agonist, belonging to the class of non-narcotic analgesics, with analgesic and sedative effects. It is the enantiomer of levomedetomidine. Dexmedetomidine is an alpha-2 adrenergic receptor agonist used in veterinary medicine for its analgesic and sedative effects. It is the racemic mixture of dexmedetomidine. Dexmedetomidine is a centrally acting alpha-2 adrenergic agonist. The mechanism of action of dexmedetomidine is as an alpha-adrenergic agonist. The physiological effects of dexmedetomidine are achieved through general anesthesia. Dexmedetomidine is an imidazole derivative, the active d-isomer of medetomidine, with analgesic, anxiolytic, and sedative effects. Dexmedetomidine selectively binds to presynaptic alpha-2 adrenergic receptors in the brain, thereby inhibiting the release of norepinephrine from synaptic vesicles. This leads to inhibition of postsynaptic adrenergic receptor activation, which in turn inhibits sympathetic nerve activity, ultimately producing sedative and anxiolytic effects. The analgesic effect of this drug is achieved by binding to α2-adrenergic receptors in the spinal cord. It is an imidazole derivative and an agonist of adrenergic α2 receptors. It is closely related to medetomidine, which is the racemic mixture of this compound. Drug Indications Dexmedetomidine is administered intravenously for sedation in patients initially intubated and mechanically ventilated in the intensive care unit, and for sedation in non-intubated patients before and/or during surgery and other procedures. It is also available in oral or sublingual dissolving film formulations for the acute treatment of agitation caused by schizophrenia or bipolar I or II. It is indicated for adult intensive care unit patients requiring sedation, with a level of sedation not exceeding arousal to verbal stimuli (corresponding to a Richmond Agitation-Sedation Scale (RASS) 0 to -3).
For use in adult intensive care unit (ICU) patients requiring sedation, with a level of sedation not exceeding arousal to verbal stimuli (corresponding to a Richmond Agitation-Sedation Scale (RASS) 0 to -3). For use in unintubated adult patients before and/or during diagnostic or surgical procedures requiring sedation, i.e., procedural/awake sedation.
For use in dogs and cats for non-invasive, mild to moderate pain examinations and procedures 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. For use in dogs and cats as a pre-treatment before induction and maintenance of general anesthesia.
For use in dogs and cats for non-invasive, mild to moderate pain examinations and procedures 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. For use in dogs and cats as a pre-treatment before induction and maintenance of general anesthesia.
Suitable for non-invasive, mild to moderate pain examinations and procedures in dogs and cats requiring restraint, sedation, and analgesia. Pre-treatment for cats before induction and maintenance of general anesthesia with ketamine. For dogs, when used in combination with butorphanol, it provides deep sedation and analgesia for medical and minor surgical procedures. Pre-treatment for dogs before induction and maintenance of general anesthesia.
Relieves acute anxiety and fear in dogs caused by noise.
Mechanism of Action

Dexmedetomidine is a specific and selective α2-adrenergic receptor agonist. It terminates pain signal transmission by binding to presynaptic α2-adrenergic receptors and inhibiting the release of norepinephrine. Activation of postsynaptic α2-adrenergic receptors inhibits sympathetic nerve activity, lowering blood pressure and heart rate.

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Pharmacodynamics
Dexmedetomidine activates α2-adrenergic receptors, reduces sympathetic tone, and weakens neuroendocrine and hemodynamic responses induced by anesthesia and surgery; it also reduces the need for anesthetics and opioids; dexmedetomidine can cause sedation and analgesia.

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Dexmedetomidine is the active (S)-enantiomer of medetomidine, which has an affinity for α2-adrenergic receptors that is 8-10 times higher than that for the (R)-enantiomer[1]
- This drug exerts sedative, analgesic, and anxiolytic effects by activating central α2-adrenergic receptors (mainly the α2A subtype) in the locus coeruleus, thereby reducing the release of norepinephrine[2]
- Clinically, it is approved for sedation in ICU intubated/mechanically ventilated patients, procedural sedation in non-intubated patients, and preoperative administration in children and adults[2,3]
- Dexmedetomidine can maintain respiratory function at therapeutic doses, and is therefore suitable for sedation in patients at risk of respiratory impairment.[3]

C13H16N2

200.28

200.131

C, 77.96; H, 8.05; N, 13.99

113775-47-6

Medetomidine; 86347-14-0;Dexmedetomidine hydrochloride; 145108-58-3; Medetomidine hydrochloride; 86347-15-1

5311068

White to off-white solid powder

1.053g/cm3

381.9ºC at 760mmHg

146-149°C

191.3ºC

1.08E-05mmHg at 25°C

1.569

3.178

1

1

2

15

205

1

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]

CUHVIMMYOGQXCV-NSHDSACASA-N

InChI=1S/C13H16N2/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)/t11-/m0/s1

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

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: This product requires protection from light (avoid light exposure) during transportation and storage.

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 (10.39 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 (10.39 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 (10.39 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.)