Disease relevance of Atipamezole

• Subcutaneous atipamezole, 0.06 mg/kg, reversed laparotomy-induced ileus completely [1].
• BACKGROUND AND PURPOSE: The purpose of this study was to determine whether an enriched housing environment and/or systemic administration of the alpha2-adrenergic receptor antagonist atipamezole facilitate the rate of spatial learning after global ischemia in rats [2].
• An alpha(2)-adrenergic antagonist, atipamezole, facilitates behavioral recovery after focal cerebral ischemia in rats [3].
• L 659,066 (1-10 mg/kg) had no effect on the hypothermia induced by ethanol (2 g/kg) or ethanol ataxia (2.4 g/kg), whereas atipamezole (1 mg/kg) significantly attenuated both ethanol-induced hypothermia and ataxia [4].
• This antinociceptive effect was blocked by pertussis toxin and by the alpha(2) antagonists atipamezole and L659,066 placed in the LC [5].

Psychiatry related information on Atipamezole

• The administration of atipamezole (300 micrograms/kg), a selective antagonist of alpha 2-adrenoceptors, enhanced locomotor activity compared to saline-treated rats, but these effects did not differ between the TMT group and their controls [6].
• METHODS: Male mice were administered either prazosin, betaxolol, atipamezole, corticosterone, or repeated restraint stress prior to measurement of either nest-leaving or TST [7].
• Although the highly selective alpha-2 receptor antagonist, atipamezole (ATI), failed to affect spatial working memory on its own, at the doses studied (0.1-0.5 mg/kg, s.c.), it dramatically enhanced the working memory deficit produced by PCP [8].
• Conversely, atipamezole administered intrathecally, but not intracerebroventricularly, blocked the enhanced tail-flick latency response to N2O [9].
• The present study investigated the effects of dexmedetomidine (an alpha-2 adrenoceptor agonist), atipamezole (an alpha-2 adrenoceptor antagonist) and tacrine (an inhibitor of acetylcholinesterase) on the performance of adult and aged rats in a delayed non-matching to position task assessing spatial short-term memory [10].

High impact information on Atipamezole

• OBJECTIVE: To evaluate the pharmacokinetics, systemic effects and clinical applicability of buccally administered atipamezole in healthy volunteers [11].
• In the first part, spray preparations of atipamezole hydrochloride in water/alcohol (50/50) solution were applied on buccal mucosa of six volunteers [11].
• The effect of locally infused and systemically injected alpha2-AR agonist, dexmedetomidine (DMT), and alpha2-AR antagonist, atipamezole, on NA and DA release was investigated in alpha2A-AR knockout and control mice by using in vivo microdialysis [12].
• In experiment 2, we then tested effects of microinjecting alpha1- or beta-adrenergic receptor antagonists into medial prefrontal cortex on the enhancement of performance on the extradimensional task produced by atipamezole [13].
• Metabolism of brain monoamine neurotransmitters, locomotor activity and body temperature were investigated in mice with targeted inactivation of the gene encoding alpha(2A)-AR (alpha(2A)-knockout, alpha(2A)-KO) and wild-type (WT) mice after treatment with the alpha(2)-AR agonist dexmedetomidine and the antagonist atipamezole [14].

Chemical compound and disease context of Atipamezole

• Dexmedetomidine improves neurologic outcome from incomplete ischemia in the rat. Reversal by the alpha 2-adrenergic antagonist atipamezole [15].
• In awake rats treated chronically with clonidine, atipamezole did not change MAP but produced arterial pressure lability and tachycardia [16].
• This was accomplished by measuring the reaction and movement times of monkeys performing a visual choice reaction time task under the influence of medetomidine or its antagonist atipamezole [17].
• Antagonistic effect of atipamezole on xylazine-induced sedation, bradycardia, and ruminal atony in calves [18].
• Twenty-five mins later, each horse received one of 4 treatments: Group 1 saline (0.9% i.v.) as a placebo control; Group 2 atipamezole (0.05 mg/kg bwt i.v.); Group 3 atipamezole (0.1 mg/kg bwt i.v.); and Group 4 tolazoline (4.0 mg/kg bwt i.v.). Sedation, muscle relaxation and ataxia were scored by 3 independent observers at 9 time points [19].

Biological context of Atipamezole

• Atipamezole dose dependently reversed the reductions in blood pressure (P < 0.001) and heart rate (P = 0.009) [20].
• 2. Atipamezole (1 and 3 mg kg-1) alone had no effect on body temperature but significantly attenuated the 8-OH-DPAT-induced hypothermic response [21].
• Atipamezole slightly increased food intake and neuropeptide Y content in the paraventricular hypothalamic nucleus but had no effect on the other measured parameters [22].
• Neither atipamezole (0.3 mg/kg s.c.) nor idazoxan (1 mg/kg s.c.) had any effect on blood pressure when given alone, but reversed the apomorphine-induced decrease in blood pressure [23].
• The present experiments investigated the effects of a specific and potent alpha(2)-adrenoceptor antagonist, atipamezole, on cognitive performance and neurochemistry in aged rats [24].

Anatomical context of Atipamezole

• Administration of atipamezole normalised [14C]DG uptake particularly in the cerebellum and spinal cord both in sham-operated and ischemic rats and to a lesser extent in the thalamus in sham-operated rats [25].
• 5 Atipamezole had no inhibitory effect on MAO-A or MAO-B activity in renal membranes, which speaks against the involvement of MAOs in the observed radioligand binding [26].
• The alpha 2-adrenoceptor antagonists used were, atipamezole, which occupies both central and peripheral receptors, and L 659,066, which poorly penetrates the blood brain barrier [21].
• Systemically administered medetomidine produced an atipamezole-reversible, dose-dependent suppressive effect on the evoked responses of nociceptive medial thalamic and spinothalamic tract neurons [27].
• In the present paper we have shown that local infusions of NE or of the alpha2-adrenoceptor antagonist, atipamezole, in the mouse amygdala produces localized expression of fos [28].

Associations of Atipamezole with other chemical compounds

• In the present study, the effects of an alpha 2 agonist (clonidine, 1.0 mg/kg i.p.) and two antagonists (atipamezole, 1 and 10 mg/kg s.c. and yohimbine, 3.0 mg/kg i.p.) were studied on the EEG activity of naive rats, pretreated with either saline or scopolamine (0.8 mg/kg), or rats receiving lesioning of the nucleus basalis [29].
• 2. BRL 35135 (beta 3-agonist, 0.5 mg kg-1 day-1 p.o.), atipamezole (alpha 2-antagonist, 4.0 mg kg-1 day-1 p.o.) and placebo were given to genetically obese male Zucker rats [22].
• Activation of fos in mouse amygdala by local infusion of norepinephrine or atipamezole [28].
• Local perfusion with atipamezole via the microdialysis probe increased histamine release significantly and dose-dependently [30].
• Effects of atipamezole, detomidine and medetomidine on release of steroid hormones by porcine adrenocortical cells in vitro [31].

Gene context of Atipamezole

• Phenylephrine caused ERK phosphorylation only at a concentration high enough to exert non subtype-specific effects (10 microM), and this effect was counteracted by the alpha(2)-adrenergic antagonist atipamezole [32].
• Atipamezole (1-3 mg/kg) significantly attenuated the ethanol-induced reduction in exploratory head-dipping in a holeboard test whereas L 659,066 was only effective at a dose of 1 mg/kg, higher doses (3 and 10 mg/kg) and a lower dose (0.3 mg/kg) were ineffective [4].
• Atipamezole was without effect on ethanol's locomotor stimulant effect in the holeboard but L 659,066 attenuated this effect at doses less than 3 mg/kg Many alpha-2 adrenoceptor ligands also have affinity for nonadrenergic imidazoline-binding sites [4].
• Dexmedetomidine at 100 nM added to the basolateral side of the CCD reduced AVP-stimulated Pf by 95% to 100%, and the alpha-2 antagonist atipamezole reversed the inhibition [33].
• In the arcuate, only the highest dose of atipamezole had an effect on PRL, and this was in the opposite direction from that seen in the PVN [34].

Analytical, diagnostic and therapeutic context of Atipamezole

• Sedation was quickly reversed by the administration of the antagonist atipamezole after the fMRI experiment [35].
• Atipamezole did not enhance short-term or long-term memory in either TMT or control groups [6].
• The alpha 2-adrenoceptor antagonists idazoxan (2.5 and 20 mg/kg), atipamezole (2.5 mg/kg), and fluparoxan (10 mg/kg) increased ACh outflow by up to 250-325% of basal levels over a 3-h period following intraperitoneal injection [36].
• Atipamezole alone did not alter background EEG, nor did it affect the clonic convulsant threshold [37].
• Medetomidine, a new alpha 2-adrenoceptor agonist produced dose-dependent (30-100 micrograms/kg i.p.) analgesia in the formalin test in rats, and this effect was reversed by atipamezole (1 mg/kg), a new alpha 2-adrenoceptor antagonist [38].

References