Characterization of the selectivity, specificity and potency of medetomidine as an α2-adrenoceptor agonist

Virtanen, Raimo; Savola, Juha‐Matti; Saano, Veijo; Nyman, Leena

doi:10.1016/0014-2999(88)90744-3

Cited by 650 publications

(387 citation statements)

References 17 publications

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“…In part 3, dexmedetomidine (DEX) (Precedex, Maruishi), an ␣2-adrenoceptor agonist, was infused at all sites with increasing concentration in the following order (10 Ϫ9 , 10 Ϫ8 , 10 Ϫ7 , 10 Ϫ6 , 10 Ϫ5 , and 10 Ϫ4 M), with each dose being delivered for 10 min. DEX causes more ␣2-selective vasoconstriction by the stimulation of receptors present in the vascular smooth muscle than clonidine (25,37). In part 4, isoproterenol (ISO) (Sigma), a ␤-adrenoceptor agonist, was infused at all sites with increasing concentration in the following order (10 Ϫ8 , 10 Ϫ7 , 10 Ϫ6 , 10 Ϫ5 , 10 Ϫ4 , and 10 Ϫ3 M), with each dose being delivered for 10 min.…”

Section: Subjectsmentioning

confidence: 99%

Limb-specific differences in the skin vascular responsiveness to adrenergic agonists

Yamazaki

Yuge

2011

Journal of Applied Physiology

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Yamazaki F, Yuge N. Limb-specific differences in the skin vascular responsiveness to adrenergic agonists. J Appl Physiol 111: 170-176, 2011. First published April 28, 2011 doi:10.1152/japplphysiol.00068.2011In this study, to test the hypothesis that adrenergic vasoconstrictor responses of the legs are greater compared with the arms in human skin, cutaneous vascular conductance (CVC) in the forearm and calf were compared during the infusion of adrenergic agonists in healthy young volunteers. Under normothermic conditions, norepinephrine (NE, ␣-and ␤-agonist, 1 ϫ 10 Ϫ8 to 1 ϫ 10 Ϫ2 M), phenylephrine (PHE, ␣1-agonist, 1 ϫ 10 Ϫ8 to 1 ϫ 10 Ϫ2 M), dexmedetomidine (DEX, ␣2-agonist, 1 ϫ 10 Ϫ9 to 1 ϫ 10 Ϫ4 M), and isoproterenol (ISO, ␤-agonist, 1 ϫ 10 Ϫ8 to 1 ϫ 10 Ϫ3 M) were administered by intradermal microdialysis. Skin blood flow (SkBF) was measured by laserDoppler flowmetry, and the local temperature at SkBF-measuring sites was maintained at 34°C throughout the experiments. CVC was calculated as the ratio of SkBF to blood pressure and expressed relative to the baseline value before drug infusion. The dose of NE at the onset of vasoconstriction and the effective dose (ED50) resulting in 50% of the maximal vasoconstrictor response for NE were lower (P Ͻ 0.001) in the calf than forearm. The ED50 for PHE and DEX was also lower (P Ͻ 0.05) in the calf than forearm. Increases in CVC in response to ISO were potentially smaller in the calf, but the statistical differences in the responses were dependent on the expressions of CVC. These findings suggest that the cutaneous vasoconstrictor responsiveness to exogenous NE is greater in the legs than in the arms due to a higher ␣1-and ␣2-adrenoceptor reactivity, while the ␤-adrenoceptor function plays a minor role in regional differences in adrenergic vasoconstriction in normothermic humans. skin blood flow; exogenous norepinephrine; ␣-adrenergic receptor; ␤-adrenergic receptor; microdialysis IN HUMANS, peripheral vasoconstrictor responses to upright posture show heterogeneity between the upper and lower limbs (14,16,22,48). The findings from previous studies suggest that the leg vasculature is more responsive to orthostatic stimulation than the arm vasculature. The augmented vasoconstrictor response observed in the human lower-leg vasculature is influenced by sympathetic and local mechanisms (14,22,24,38) and could play an important regulatory role by limiting the degree to which blood accumulates in the legs during orthostatic stress (29,30).The vasoconstrictor response to the upright posture is via reflex and nonreflex (e.g., venoarteriolar response) mechanisms. The reflex vasoconstriction is influenced by centrally driven activity in sympathetic vasoconstrictor nerves and postjunctional adrenergic receptor responsiveness. With regard to the central sympathetic outflow, similar increases in muscle sympathetic nerve activity have been shown in the arm and leg during orthostatic stress (14, 31). In addition, similar increases in regional norepinephrine (NE) spillover have been re...

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Section: Subjectsmentioning

confidence: 99%

Limb-specific differences in the skin vascular responsiveness to adrenergic agonists

Yamazaki

Yuge

2011

Journal of Applied Physiology

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“…Medetomidine is a selective and potent α 2 adrenoceptor agonist used for sedation and 77 analgesia in veterinary anaesthesia (Virtanen et al, 1988;Pertovaara, 1993). When administered as 78 a constant rate intravenous infusion (CRI) as a component of partial intravenous anaesthesia 79 (PIVA), it reduces the minimum alveolar concentration (MAC) of isoflurane in horses (Neges et al, 80 2003) and improves the quality of recovery (Ringer et al, 2007).…”

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Effect of low inspired oxygen fraction on respiratory indices in mechanically ventilated horses anaesthetised with isoflurane and medetomidine constant rate infusion

Taylor

Seymour

2016

The Veterinary Journal

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“…Azaperone is a neuroleptic butyrophenone commonly marketed as a tranquilizer in pigs that also has been used in a variety of wildlife (Colly, 1992;Hall et al, 2001). Medetomidine is a potent alpha 2 agonist with significant analgesia, muscle relaxation, and sedation that can be antagonized with atipamezole (MacDonald et al, 1988;Virtanen et al, 1988). Medetomidine has been used in combination with other drugs such as ketamine and butorphanol in a variety of wild animals from wood rats to gazelles (Jalanka and Roeken, 1990;Chittick et al, 2001;Larsen et al, 2002;Hahn et al, 2005); using medetomidine in combination with other drugs often reduces the total requirement (Jalanka and Roeken, 1990).…”

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confidence: 99%

Immobilization of Black Bears (Ursus americanus) with a Combination of Butorphanol, Azaperone, and Medetomidine

Wolfe

Goshorn

Baruch‐Mordo

2008

Journal of Wildlife Diseases

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ABSTRACT:Sixteen captive and five free-ranging black bears (Ursus americanus) were immobilized with a combination of butorphanol, azaperone, and medetomidine (BAM). The BAM drug combination was premixed using 0.5 ml butorphanol (30 mg/ml), 0.25 ml azaperone (50 mg/ml), and 0.25 ml medetomidine (20 mg/ml) per milliliter to yield a final mix of (15 mg butorphanol + 12.5 mg azaperone + 5 mg medetomidine)/ml. This combination, dosed at 0.4 ml BAM/,23 kg estimated body weight, provided a mean induction time of 10 min (95% confidence interval [CI] 5 2 min), consistent anesthesia without apparent adverse effects, and smooth recovery (mean 5 15 min, 95% CI 5 4 min) after antagonism with atipamezole (5 mg/mg medetomidine) alone or in combination with naltrexone (5 mg/mg butorphanol). Based on our initial observations, BAM appears to be a reversible and accessible drug combination for immobilizing black bears that merits further evaluation for field use.

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Characterization of the selectivity, specificity and potency of medetomidine as an α2-adrenoceptor agonist

Cited by 650 publications

References 17 publications

Limb-specific differences in the skin vascular responsiveness to adrenergic agonists

Limb-specific differences in the skin vascular responsiveness to adrenergic agonists

Effect of low inspired oxygen fraction on respiratory indices in mechanically ventilated horses anaesthetised with isoflurane and medetomidine constant rate infusion

Immobilization of Black Bears (Ursus americanus) with a Combination of Butorphanol, Azaperone, and Medetomidine

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