The anesthetic-reducing property of medetomidine far exceeds that seen with other alpha 2-adrenergic agonists (e.g., clonidine). This study examined whether medetomidine possesses hypnotic-anesthetic actions. Dexmedetomidine (the d-enantiomer of medetomidine) induced loss of righting reflex in rats (i.e., hypnosis) at doses greater than 100 micrograms/kg i.p.; sleep-time was dose-dependent up to 1000 micrograms/kg i.p. The l-enantiomer of medetomidine (MPV-1441) did not induce hypnosis even when administered up to 30,000 micrograms/kg i.p.
Dexmedetomidine, a highly selective and potent alpha-2 adrenoceptor agonist, reduces halothane anesthetic requirements by over 90% in rats. The present study examined whether dexmedetomidine produces a hypnotic-anesthetic action in rats. Dexmedetomidine induced a hypnotic-anesthetic state in rats characterized by loss of righting reflex at doses greater than or equal to 0.1 mg/kg. This response was dose-dependent between 0.1 and 3 mg/kg.
Dexmedetomidine, a highly selective and potent agonist at alpha-2 adrenoceptors, produces a hypnotic-anesthetic action in rats. The mechanism for this response may involve an inhibitory G-protein and increased conductance through a potassium channel. To investigate this, the effects of pertussis toxin, a specific inactivator of inhibitory G-proteins, and 4-aminopyridine, a blocker of potassium channels, on the hypnotic-anesthetic response to dexmedetomidine were studied in rats.
The effects of chronic administration of the calcium channel antagonist verapamil on the anesthetic effects of a novel specific alpha 2-receptor agonist (dexmedetomidine) were studied in rats. It is presumed that this agonist acts on both pre- and postsynaptic alpha 2-adrenoceptors. To determine whether the central postsynaptic receptors are involved in the anesthetic interactions between these drugs, rats were treated with DSP-4 to deplete endogenous norepinephrine. Loss of the righting reflex was used to determine the presence of anesthesia and the duration of hypnosis.
Previously, we demonstrated that dexmedetomidine, an alpha 2 agonist, produces a hypnotic-anesthetic response in rats via activation of central alpha 2 adrenoceptors and that this response could be enhanced by the alpha 1 antagonist prazosin. In the current experiment we investigated whether central alpha 1 adrenoceptor stimulation antagonizes the alpha 2 adrenoceptor-mediated hypnotic response.
Our study examined whether calcium channels are involved in the anesthetic action of dexmedetomidine (100-300 micrograms/kg), a highly selective alpha 2-adrenoceptor agonist. To investigate this, we studied the effects of verapamil (1.25 or 2.5 mg/kg), a calcium channel blocker, and BAY K8644 (0.5 or 1 mg/kg), a calcium channel agonist, on the hypnotic-anesthetic effect of dexmedetomidine in rats. Loss of the righting reflex was used to determine the presence of anesthesia, and its length in minutes was referred to as the duration of hypnosis.
We studied the effects of atipamezole, an alpha 2-adrenoceptor antagonist, on hypnosis induced by medetomidine, an alpha 2-adrenoceptor agonist (1 mg/kg IP), and pentobarbital (40 mg/kg IP) by testing the righting reflex in the rat. The duration of antinociception was assessed with repeated pinch tests. Medetomidine-induced hypnosis and antinociception were inhibited by atipamezole at doses greater than 0.1 mg/kg. Atipamezole restored the righting reflex at a dose ratio that was 1:10 or more to that of medetomidine used to induce hypnosis.
The role of serotonergic pathways in the hypnotic response to dexmedetomidine was examined in neurochemical and behavioral studies. Following acute administration of dexmedetomidine, loss of righting reflex and changes in serotonin (5-hydroxytryptamine, 5-HT) and norepinephrine turnover in different brain regions (locus coeruleus and hippocampus) were assessed. In separate experiments, the effect of dexmedetomidine on 5-HT turnover was measured in rats rendered tolerant to the hypnotic effects of dexmedetomidine.
The use of a combination of medetomidine and ketamine as anaesthetic for dental surgery was investigated in 60 dogs. The nature of the interventions varied from inspection of the teeth with cleaning of the teeth or simple tooth extraction to extraction of one or more dental elements or endodontic treatment. The operations lasted between 20 and 70 minutes, with an average of 34 +/- 15 minutes. Medetomidine, 1000 m g/m2 body surface administered intramuscularly, was used as premedication. Anaesthesia was induced with intravenously administered ketamine at a dose of 2-3 mg/kg body weight.
The use of a combination of medetomidine and ketamine as anaesthetic for dental surgery was investigated in 60 dogs. The nature of the interventions varied from inspection of the teeth with cleaning of the teeth or simple tooth extraction to extraction of one or more dental elements or endodontic treatment. The operations lasted between 20 and 70 minutes, with an average of 34 +/- 15 minutes. Medetomidine, 1000 micrograms/m2 body surface administered intramuscularly, was used as premedication.