Vatinoxan hydrochloride (MK-467 hydrochloride)
(Synonyms: MK-467 hydrochloride; L-659066 hydrochloride) 目录号 : GC30938
Vatinoxan hydrochloride (MK-467 hydrochloride) (MK-467 hydrochloride;L-659066 hydrochloride) 是一种外周 α2 肾上腺素能受体拮抗剂。
Cas No.:130466-38-5
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Animal experiment: | Dogs[1]Eight dogs receive either dexmedetomidine (10 μg/kg), Vatinoxan (250 μg/kg or dexmedetomidine (10 μg/kg) with increasing doses of Vatinoxan (250 μg/kg, 500 μg/kg and 750 μg/kg). Treatments are given intravenously (i.v.) in a randomized, crossover design with a 14-day ishout period. Systemic hemodynamics and arterial blood gas analyses are recorded at baseline and at intervals up to 90 min after drugs administration[1].Cats[2]Cats are administered seven IV treatments are administered at least 2 weeks apart, consisting of dexmedetomidine 12.5 μg/kg (D12.5) and 25 μg/kg (D25), Vatinoxan 300 μg/kg (M300), and D25 combined with 75, 150, 300 and 600 μg/kg of Vatinoxan (D25M 75, D25M150, D25M300 and D25M600, respectively). Heart rates (HR) are recorded via telemetry and sedation assessed with a simple descriptive score and a visual analogue scale prior to treatments and at intervals until 8 hours thereafter[2]. |
References: [1]. Honkavaara JM, et al. The effects of increasing doses of MK-467, a peripheral alpha(2)-adrenergic receptor antagonist, on the cardiopulmonary effects of intravenous dexmedetomidine in conscious dogs. J Vet Pharmacol Ther. 2011 Aug;34(4):332-7. | |
Vatinoxan hydrochloride (MK-467 hydrochloride;L-659066 hydrochloride) is a peripheral α2 adrenergic receptor antagonist.
Vatinoxan alone increases cardiac index and tissue oxygen delivery and has no deleterious adverse effects. Vatinoxan attenuates or prevents dexmedetomidine’s systemic hemodynamic effects in a dose-dependent manner when given simultaneously i.v. but has no effect on the pulmonary outcome in conscious dogs. A 50:1 dose ratio (Vatinoxan:dexmedetomidine) induces the least alterations in cardiovascular function[1]. Vatinoxan dose-dependently attenuates the bradycardia associated with dexmedetomidine, and shortens the sedative effect without altering its quality. Vatinoxan may be useful in attenuating reductions in heart rate in conscious catsadministered dexmedetomidine[2].
[1]. Honkavaara JM, et al. The effects of increasing doses of MK-467, a peripheral alpha(2)-adrenergic receptor antagonist, on the cardiopulmonary effects of intravenous dexmedetomidine in conscious dogs. J Vet Pharmacol Ther. 2011 Aug;34(4):332-7. [2]. Honkavaara J, et al. The effect of MK-467, a peripheral α2-adrenoceptor antagonist, on dexmedetomidine-inducedsedation and bradycardia after intravenous administration in conscious cats. Vet Anaesth Analg. 2017 Feb 22. pii: S1467-2987(16)31387-3.
| Cas No. | 130466-38-5 | SDF | |
| 别名 | MK-467 hydrochloride; L-659066 hydrochloride | ||
| 化学名 | N-(2-((2R,12bS)-2'-oxo-1,3,4,6,7,12b-hexahydrospiro[benzofuro[2,3-a]quinolizine-2,4'-imidazolidin]-3'-yl)ethyl)methanesulfonamide hydrochloride | ||
| Canonical SMILES | [H]Cl.CS(=O)(NCCN([C@]1(CN2)CCN3CCC4=C(OC5=CC=CC=C54)[C@]3([H])C1)C2=O)=O | ||
| 分子式 | C20H27ClN4O4S | 分子量 | 454.97 |
| 溶解度 | Water : ≥ 133 mg/mL (292.33 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.1979 mL | 10.9897 mL | 21.9795 mL |
| 5 mM | 0.4396 mL | 2.1979 mL | 4.3959 mL |
| 10 mM | 0.2198 mL | 1.099 mL | 2.1979 mL |
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动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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Cardiovascular effects of intravenous vatinoxan (MK-467) in medetomidine-tiletamine-zolazepam anaesthetised red deer (Cervus elaphus)
Objective: To determine the effect of intravenous vatinoxan administration on bradycardia, hypertension and level of anaesthesia induced by medetomidine-tiletamine-zolazepam in red deer (Cervus elaphus). Study design and animals: A total of 10 healthy red deer were included in a randomised, controlled, experimental, crossover study. Methods: Deer were administered a combination of 0.1 mg kg-1 medetomidine hydrochloride and 2.5 mg kg-1 tiletamine-zolazepam intramuscularly, followed by 0.1 mg kg-1 vatinoxan hydrochloride or equivalent volume of saline intravenously (IV) 35 minutes after anaesthetic induction. Heart rate (HR), mean arterial blood pressure (MAP), respiration rate (fR), end-tidal CO2 (Pe'CO2), arterial oxygen saturation (SpO2), rectal temperature (RT) and level of anaesthesia were assessed before saline/vatinoxan administration (baseline) and at intervals for 25 minutes thereafter. Differences within treatments (change from baseline) and between treatments were analysed with linear mixed effect models (p < 0.05). Results: Maximal (81 ± 10 beats minute-1) HR occurred 90 seconds after vatinoxan injection and remained significantly above baseline (42 ± 4 beats minute-1) for 15 minutes. MAP significantly decreased from baseline (122 ± 10 mmHg) to a minimum MAP of 83 ± 6 mmHg 60 seconds after vatinoxan and remained below baseline until end of anaesthesia. HR remained unchanged from baseline (43 ± 5 beats minute-1) with the saline treatment, whereas MAP decreased significantly (112 ± 16 mmHg) from baseline after 20 minutes. Pe'CO2, fR and SpO2 showed no significant differences between treatments, whereas RT decreased significantly 25 minutes after vatinoxan. Level of anaesthesia was not significantly influenced by vatinoxan. Conclusions and clinical relevance: Vatinoxan reversed hypertension and bradycardia induced by medetomidine without causing hypotension or affecting the level of anaesthesia in red deer. However, the effect on HR subsided 15 minutes after vatinoxan IV administration. Vatinoxan has the potential to reduce anaesthetic side effects in non-domestic ruminants immobilised with medetomidine-tiletamine-zolazepam.
Effects of MK-467 hydrochloride and hyoscine butylbromide on cardiorespiratory and gastrointestinal changes induced by detomidine hydrochloride in horses
OBJECTIVE To compare the effects of MK-467 and hyoscine butylbromide on detomidine hydrochloride-induced cardiorespiratory and gastrointestinal changes in horses. ANIMALS 6 healthy adult horses. PROCEDURES Horses received detomidine hydrochloride (20 μg/kg, IV), followed 10 minutes later by MK-467 hydrochloride (150 μg/kg; DET-MK), hyoscine butylbromide (0.2 mg/kg; DET-HYO), or saline (0.9% NaCl) solution (DET-S), IV, in a Latin square design. Heart rate, respiratory rate, rectal temperature, arterial and venous blood pressures, and cardiac output were measured; blood gases and arterial plasma drug concentrations were analyzed; selected cardiopulmonary variables were calculated; and sedation and gastrointestinal borborygmi were scored at predetermined time points. Differences among treatments or within treatments over time were analyzed statistically. RESULTS With DET-MK, detomidine-induced hypertension and bradycardia were reversed shortly after MK-467 injection. Marked tachycardia and hypertension were observed with DET-HYO. Mean heart rate and mean arterial blood pressure differed significantly among all treatments from 15 to 35 and 15 to 40 minutes after detomidine injection, respectively. Cardiac output was greater with DET-MK and DET-HYO than with DET-S 15 minutes after detomidine injection, but left ventricular workload was significantly higher with DET-HYO. Borborygmus score, reduced with all treatments, was most rapidly restored with DET-MK. Sedation scores and pharmacokinetic parameters of detomidine did not differ between DET-S and DET-MK. CONCLUSIONS AND CLINICAL RELEVANCE MK-467 reversed or attenuated cardiovascular and gastrointestinal effects of detomidine without notable adverse effects or alterations in detomidine-induced sedation in horses. Further research is needed to determine whether these advantages are found in clinical patients and to assess whether the drug influences analgesic effects of detomidine.
Cardiovascular and sedation reversal effects of intramuscular administration of atipamezole in dogs treated with medetomidine hydrochloride with or without the peripheral α2-adrenoceptor antagonist vatinoxan hydrochloride
Objective: To investigate the cardiovascular and sedation reversal effects of IM administration of atipamezole (AA) in dogs treated with medetomidine hydrochloride (MED) or MED and vatinoxan (MK-467).
Animals: 8 purpose-bred, 2-year-old Beagles.
Procedures: A randomized, blinded, crossover study was performed in which each dog received 2 IM treatments at a ≥ 2-week interval as follows: injection of MED (20 μg/kg) or MED mixed with 400 μg of vatinoxan/kg (MEDVAT) 30 minutes before AA (100 μg/kg). Sedation score, heart rate, mean arterial and central venous blood pressures, and cardiac output were recorded before and at various time points (up to 90 minutes) after AA. Cardiac and systemic vascular resistance indices were calculated. Venous blood samples were collected at intervals until 210 minutes after AA for drug concentration analysis.
Results: Heart rate following MED administration was lower, compared with findings after MEDVAT administration, prior to and at ≥ 10 minutes after AA. Mean arterial blood pressure was lower with MEDVAT than with MED at 5 minutes after AA, when its nadir was detected. Overall, cardiac index was higher and systemic vascular resistance index lower, indicating better cardiovascular function, in MEDVAT-atipamezole-treated dogs. Plasma dexmedetomidine concentrations were lower and recoveries from sedation were faster and more complete after MEDVAT treatment with AA than after MED treatment with AA.
Conclusions and clinical relevance: Atipamezole failed to restore heart rate and cardiac index in medetomidine-sedated dogs, and relapses into sedation were observed. Coadministration of vatinoxan with MED helped to maintain hemodynamic function and hastened the recovery from sedation after AA in dogs.
The impact of vatinoxan on medetomidine-ketamine-midazolam immobilization in Patagonian maras (Dolichotis patagonum)
Objective: To compare cardiovascular and ventilatory effects, immobilization quality and effects on tissue perfusion of a medetomidine-ketamine-midazolam combination with or without vatinoxan (MK-467), a peripherally acting α2-adrenoceptor antagonist.
Study design: Randomized, blinded, crossover study.
Animals: A group of nine healthy Patagonian maras (Dolichotis patagonum).
Methods: Maras were immobilized twice with: 1) medetomidine hydrochloride (0.1 mg kg-1) + ketamine (5 mg kg-1) + midazolam (0.1 mg kg-1) (MKM) + saline or 2) MKM + vatinoxan hydrochloride (0.8 mg kg-1), administered intramuscularly. Drugs were mixed in the same syringe. At 20, 30 and 40 minutes after injection, invasive blood pressure, heart rate, respiration rate, end-tidal CO2, haemoglobin oxygen saturation, and muscle oxygenation were measured, arteriovenous oxygen content difference was calculated. Muscle tone, jaw tone, spontaneous blinking and palpebral reflex were evaluated. Times to initial effect, recumbency, initial arousal and control of the head were recorded. Paired t test, Wilcoxon matched-pairs signed rank test and analysis of variance were used to compare protocols; (p < 0.05).
Results: Vatinoxan significantly reduced systolic (p = 0.0002), mean (MAP; p < 0.0001) and diastolic (p < 0.0001) arterial blood pressures between 20 and 40 minutes. MAPs at 30 minutes (mean ± standard deviation) with MKM and MKM + vatinoxan were 105 ± 12 and 71 ± 14 mmHg, respectively. Without vatinoxan, four animals were hypertensive (MAP > 120 mmHg), whereas with vatinoxan, four animals were hypotensive (MAP < 60 mmHg). Muscle and jaw tone were significantly more frequently present with MKM (both p = 0.039). Other measurements did not significantly differ between protocols.
Conclusions and clinical relevance: In Patagonian maras, vatinoxan attenuated the increase in blood pressure induced by medetomidine. Muscle and jaw tone were more frequently present with MKM, indicating that quality of immobilization with vatinoxan was more profound.
Cardiovascular effects of dobutamine, norepinephrine and phenylephrine in isoflurane-anaesthetized dogs administered dexmedetomidine-vatinoxan
Objective: To determine whether dobutamine, norepinephrine or phenylephrine infusions alleviate hypotension in isoflurane-anaesthetized dogs administered dexmedetomidine with vatinoxan.
Study design: Balanced, randomized crossover trial.
Animals: A total of eight healthy Beagle dogs.
Methods: Each dog was anaesthetized with isoflurane (end-tidal isoflurane 1.3%) and five treatments: dexmedetomidine hydrochloride (2.5 μg kg-1) bolus followed by 0.9% saline infusion (DEX-S); dexmedetomidine and vatinoxan hydrochloride (100 μg kg-1) bolus followed by an infusion of 0.9% saline (DEX-VAT-S), dobutamine (DEX-VAT-D), norepinephrine (DEX-VAT-N) or phenylephrine (DEX-VAT-P). The dexmedetomidine and vatinoxan boluses were administered at baseline (T0) and the treatment infusion was started after 15 minutes (T15) if mean arterial pressure (MAP) was < 90 mmHg. The treatment infusion rate was adjusted every 5 minutes as required. Systemic haemodynamics were recorded at T0 and 10 (T10) and 45 (T45) minutes. A repeated measures analysis of covariance model was used.
Results: Most dogs had a MAP < 70 mmHg at T0 before treatment. Treatments DEX-S and DEX-VAT all significantly increased MAP at T10, but systemic vascular resistance index (SVRI) was significantly higher and cardiac index (CI) lower after DEX-S than after DEX-VAT. CI did not significantly differ between DEX-S and DEX-VAT-S at T45, while SVRI remained higher with DEX-S. Normotension was achieved by all vasoactive infusions in every dog, whereas MAP was below baseline with DEX-VAT-S, and higher than baseline with DEX-S at T45. Median infusion rates were 3.75, 0.25 and 0.5 μg kg-1 minute-1 for dobutamine, norepinephrine and phenylephrine, respectively. Dobutamine and norepinephrine increased CI (mean ± standard deviation, 3.35 ± 0.70 and 3.97 ± 1.24 L minute-1 m-2, respectively) and decreased SVRI, whereas phenylephrine had the opposite effect (CI 2.13 ± 0.45 L minute-1 m-2).
Conclusions and clinical relevance: Hypotension in isoflurane-anaesthetized dogs administered dexmedetomidine and vatinoxan can be treated with either dobutamine or norepinephrine.