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M Maze

Publications and source records attributed to M Maze.

At least 91 records · Page 5Linked to original sources
PubMed1991

Clinical efficacy of oral-transdermal clonidine combinations during the perioperative period.

In an attempt to maintain stable levels of an alpha 2-adrenergic agonist throughout the perioperative period, two different oral-transdermal clonidine dosage regimens were administered according to a randomized, double-blind, placebo-controlled study in patients undergoing abdominal surgery. We determined the clinical efficacy of a high- and a low-dose clonidine regimen on sedation, hemodynamic parameters, anesthesia, and analgesia. The low-dose clonidine group of patients (n = 14) received a 7-cm2 clonidine transdermal patch (Catapres-TTS #2), which was supplemented with oral doses of clonidine approximately 3 micrograms.kg-1 on the evening prior to surgery and on the morning of surgery. The high-dose clonidine group (n = 14) received a 10.5-cm2 clonidine transdermal patch (Catapres-TTS #3) with oral clonidine approximately 4.5 micrograms.kg-1 at bedtime and 6.0 micrograms.kg-1 on the morning of surgery. Placebo-treated (control) patients received the same occlusive patch without active ingredient and oral placebo tablets at bedtime and on the morning of surgery. Preanesthetic medication included midazolam 50 micrograms.kg-1 intramuscularly (im). Anesthesia was induced with alfentanil 30 micrograms.kg-1 intravenously (iv), thiopental 3 mg.kg-1 iv, and vecuronium 0.1 mg.kg-1 iv, and was maintained with 70% nitrous oxide in oxygen and a continuous infusion of alfentanil 0.5 microgram.kg-1.min-1. Isoflurane was added when the blood pressure exceeded 110% of the patient's prestudy value. For pain relief postoperatively, the patients received morphine, 1-2-mg iv boluses, via a patient-controlled analgesia pump. The low-dose clonidine patient group had mean plasma clonidine concentrations that varied from 1.47 ng.ml-1 (preoperative) to 1.32 ng.ml-1 (postoperative day 2).(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Anesthesia↗
PubMed1991

Dexmedetomidine prevents epinephrine-induced arrhythmias through stimulation of central alpha 2 adrenoceptors in halothane-anesthetized dogs.

Since alpha 2-adrenergic agonists have important effects on the adrenergic system that have recently been applied to the anesthetic setting, we investigated the effect of stimulation of alpha 2 adrenoceptors on epinephrine-induced arrhythmias in halothane-anesthetized dogs. The arrhythmogenic threshold for epinephrine was determined during halothane anesthesia in the presence of dexmedetomidine, a selective alpha 2 agonist, and L-medetomidine, a stereoisomer of medetomidine that lacks alpha 2-agonist activity. Dexmedetomidine increased the arrhythmogenic threshold for epinephrine in a dose-dependent manner during halothane anesthesia. At the highest dose of dexmedetomidine, 0.5 microgram.kg-1.min-1, there was a three-fold increase in both the arrhythmogenic dose of epinephrine and the plasma epinephrine concentration that was reached at this dose. On the other hand, L-medetomidine over the same dose range did not effect the arrhythmogenic dose of epinephrine. Atipamezole, a central alpha 2 antagonist that crossed the blood-brain barrier, blocked the antiarrhythmic action of dexmedetomidine. L-659,066 a peripheral alpha 2 antagonist that does not penetrate the blood-brain barrier, did not affect the antiarrhythmic action of dexmedetomidine. Thus, dexmedetomidine's antiarrhythmic effect on epinephrine-induced arrhythmias during halothane anesthesia appears to be mediated at least in part by stimulation of central alpha 2 adrenoceptors.

Adrenergic alpha-Agonists↗
PubMed1991

Central alpha 1-adrenoceptor stimulation functionally antagonizes the hypnotic response to dexmedetomidine, an alpha 2-adrenoceptor agonist.

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. Cirazoline, an alpha 1 adrenoceptor agonist that partitions into the central nervous system, attenuated dexmedetomidine's hypnotic response whether administered systemically (0.3-1 mg.kg-1 intraperitoneally [ip]) or centrally (0.1 mg.kg-1 intracerebroventricularly). Prazosin, an alpha 1 adrenoceptor antagonist that effectively crosses the blood-brain barrier, fully blocked cirazoline's attenuating effect on dexmedetomidine-induced hypnosis, whereas doxazosin, which partitions poorly into the brain, did not block cirazoline's effect. Administration of phenylephrine, 0.3-3 mg.kg-1 ip, an alpha 1 adrenoceptor agonist that does not penetrate into the brain, did not attenuate dexmedetomidine's hypnotic effect. These results indicate that central alpha 1-adrenoceptor stimulation functionally antagonizes the hypnotic response to an alpha 2-adrenoceptor agonist. These data underscore the important requirement for alpha 2 adrenoceptor selectivity if these agonists are to be useful in the anesthetic setting.

Adrenergic alpha-Agonists↗
PubMed1991

Isoflurane and an alpha 2-adrenoceptor agonist suppress nociceptive neurotransmission in neonatal rat spinal cord.

Analgesia is an important component of general anesthesia. alpha 2-adrenoceptor agonists such as clonidine and dexmedetomidine are effective analgesics at the spinal level, and furthermore, they reduce the volatile anesthetic requirement. In order to probe a possible spinal-level contribution to general anesthetic-induced analgesia, the effects of dexmedetomidine were tested in an isolated spinal cord preparation. The effects of dexmedetomidine were compared with those of isoflurane, and dexmedetomidine-isoflurane interactions were explored. The test response was a nociceptive-related slow ventral root potential (slow VRP) recorded from the isolated neonatal rat spinal cord in response to electrical stimulation of a dorsal root. At 0.2-1.28 vol%, isoflurane reversibly depressed the slow VRP. At a lower concentration (0.14 vol%), isoflurane increased the slow VRP in three of five preparations. At 1.0-1.28 vol%, isoflurane also depressed the monosynaptic reflex. Recovery on washout usually was to a level greater than control. The N-methyl-D-aspartate (NMDA) receptor antagonist (DL)-2-amino 5-phosphonovalerate (10 microM) prevented the rebound to levels above control on isoflurane washout. The earlier components of the slow VRP were more sensitive to isoflurane than were the later. Dexmedetomidine (0.5-10 nM) depressed the slow VRP and had no effect on the monosynaptic reflex. The slow VRP depends on both substance P and glutamate NMDA-receptor-mediated neurotransmission; isoflurance and dexmedetomidine depressed responses to both substance P and NMDA. Although the two agents depress responses to the same neurotransmitters, there is no evidence that they act at the same cellular site(s). There was no significant interaction between dexmedetomidine and isoflurane. The results suggest that isoflurane exerts marked inhibitory effects on spinal neurotransmission, depressing both substance P and glutamate-mediated pathways. There is a possible biphasic effect on the NMDA receptor. To the extent that nociception depends on these neurotransmitters, isoflurane may be expected to exert profound analgesic effects at the spinal level. By blocking responses to strongly arousing stimuli, these effects may contribute to general anesthesia. Suppression of nociceptive neurotransmission at the spinal level may contribute to dexmedetomidine's anesthetic-sparing properties as well as to analgesia by this agent.

Adrenergic alpha-Agonists↗
PubMed1991

Role of signal transduction in anesthetic action. Alpha 2 adrenergic agonists.

The molecular mechanism for general anesthetic action is not known. The alpha 2 adrenergic agonists represent a novel class of "anesthetic-like" agent because of their selectivity for receptor binding sites and because the transmembrane signaling systems mediating their biologic responses in non-CNS systems are known. We have begun to characterize the signal transduction pathway involved in the anesthetic-like action of the alpha 2 adrenergic agonists. The alpha 2 adrenergic agonists potently decrease both central noradrenergic neurotransmission and halothane anesthetic requirements (MAC). Since MAC is only reduced by 30-40% when noradrenergic neurotransmission is totally abolished and since the reduction in MAC with the highly selective alpha 2 adrenergic agonists exceeds 90%, factors in addition to noradrenergic neurotransmission must be contributing to the anesthetic action of the alpha 2 agonists. Studies with the superselective alpha 2 agonist dexmedetomidine confirmed this, as the alpha 2 agonist could still reduce the MAC for halothane in rats depleted of their central norepinephrine stores. The profound reduction in anesthetic requirements with dexmedetomidine raised the possibility that alpha 2 adrenergic agonists may be considered an anesthetic hypnotic agent by itself. This sole anesthetic hypnotic response was established together with the confirmation that a central alpha 2 adrenoceptor mediated this action. Subsequently, data using molecular biologic techniques suggested that the alpha 2 C4 isoreceptor was the probable receptor that mediated the anesthetic response. We further explored the postreceptor effector mechanism for the signal transduction pathway for alpha 2 anesthetic action and identified the participation of two other molecular components, namely, a pertussis-toxin-sensitive G protein and a 4-aminopyridine-sensitive ion channel. Whether the signal transduction pathway for alpha 2 anesthetic action mediates the further response to other non-alpha 2 anesthetic agents needs to be defined.

Adrenergic alpha-Agonists↗
PubMed1991

Analysis of anesthetic action on the potassium channels of the Shaker mutant of Drosophila.

Recent evidence suggest that exposure to volatile anesthetic agents causes a change in conductance through an undelineated potassium channel. With recently developed genetic and molecular techniques the Drosophila melanogaster (D.m.) genome can be manipulated to study the role that potassium ion channel function plays in anesthetic action. The IA potassium channel is encoded by the Shaker (Sh) locus on the X chromosome of D.m. Because this channel may be one of those involved in volatile anesthetic action, we tested the sensitivity to isoflurane in three Shaker strains with different degrees of dysfunctional IA conductance (Shnull greater than ShKS133 greater than Sh5). Anesthetic sensitivity was also examined in mutant strains of D.m. which express abnormalities either in other potassium channel conductances (eag, slo) or other ion conductances (para). The normally conducting wild type served as the control. Two-day-old adult D.m. were stimulated with a heat source during exposure to the volatile anesthetic isoflurane, and the number moving in response to the noxious stimulus was noted. After testing the Shaker and control strains at no fewer than 13 concentrations, the IC50S (isoflurane concentration in percent vol/vol at which 50% of the flies did not respond to the heat stimulus) were derived. The IC50 values for Sh 5 (0.89), Sh133 (1.29), and Shnull (1.37) were significantly different from the wild type (0.56). The rank order of insensitivity of these Shaker mutants corresponded to the extent of the alteration in IA conductance as established by previous studies in these mutants. Neither eag (0.66), para (0.48), nor slo (0.63) differed significantly from the wild type. These data suggest that the IA potassium channel plays a role in volatile anesthetic action.

Animals↗
PubMed1991

Effects of dexmedetomidine, a novel imidazole sedative-anesthetic agent, on adrenal steroidogenesis: in vivo and in vitro studies.

Inhibition of steroidogenesis may be produced perioperatively by imidazole compounds, such as the hypnotic agent etomidate, with potentially serious consequences for patient morbidity and mortality. Dexmedetomidine, ([+]4-[1-[2,3-dimethylphenyl]-ethyl]-1H-imidazole), another imidazole compound with anesthetic like properties, is now being used perioperatively. Therefore, we investigated the effects of dexmedetomidine on steroidogenesis as well as on binding to glucocorticoid receptors in a series of in vitro and in vivo animal studies. The effect of dexmedetomidine, 10(-8)-10(-3) M, on adrenocorticotrophic hormone (ACTH) stimulated release of corticosterone was assessed in isolated rat adrenal cells. To characterize dexmedetomidine interactions with the glucocorticoid receptor, dexmedetomidine's ability to compete for [3H]dexmethasone binding sites was studied in renal tubular cells. The effect of dexmedetomidine, 80 micrograms/kg subcutaneously, on ACTH-stimulated release of cortisol was studied in separate cohorts of dogs at various time intervals during and after anesthesia was given. To compare the inhibitory effects of etomidate and dexmedetomidine on steroidogenesis, ACTH-stimulated release of cortisol was studied in dogs treated with anesthetic doses of either dexmedetomidine (80 micrograms/kg IV) or etomidate (1 mg/kg IV). Finally, dogs were given dexmedetomidine by continuous subcutaneous infusion for 7 days at sedative doses after which their cortisol response to ACTH was determined. At dexmedetomidine concentrations greater than 10(-7) M, a dose-dependent inhibition of corticosterone release was detected in response to ACTH stimulation in vitro. At these high dexmedetomidine concentrations, [3H]dexamethasone binding was not affected. In the in vivo dog experiments, basal cortisol levels decreased and the cortisol response to ACTH was blunted 3 h after dexmedetomidine administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex↗
PubMed1991

Functional effects of activation of alpha-1 adrenoceptors by dexmedetomidine: in vivo and in vitro studies.

Dexmedetomidine, an alpha-2 adrenoceptor (AR) agonist, produces a biphasic hypnotic response in rats. Since central alpha-1 AR stimulation may reverse the hypnotic response produced by central alpha-2 AR stimulation, we have investigated, in both in vivo and in vitro models, the functional effects of dexmedetomidine on alpha-1 AR. For in vivo studies, stainless steel cannulas were inserted stereotaxically into the lateral ventricle of halothane-anesthetized rats to facilitate i.c.v. drug administration. Four to 7 days later, the alpha-1 AR antagonist prazosin (1 mg/kg-1) or saline was administered i.p. 15 min before i.c.v. injections of dexmedetomidine (10-333 micrograms) and the sleep-time (duration of loss of righting reflex) was assessed. The sleep-time increased, in a linear fashion, up to 33 micrograms; above this dose, there was a decrease in sleep-time. Pretreatment with prazosin prevented the decrease in sleep-time which was seen at higher doses. For in vitro studies, binding parameters of dexmedetomidine and its anesthetically inert L-isomer were determined from competition binding curves using [125I]2-[beta-(4-hydroxy-3-[125I]iodo- phenyl)ethylaminomethyl]-tetralone as the radiolabeled ligand and membranes prepared from HeLa cell lines stably expressing either alpha-1B or alpha-1C AR subtypes. Dexmedetomidine bound with equal affinity to both the alpha-1B (1178 +/- 63 nM) and the alpha-1C (1344 +/- 230 nM) isoreceptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists↗
PubMed1990

Modulating role of dopamine on anesthetic requirements.

The influence of dopamine on halothane anesthetic requirements was determined in mice. Halothane anesthetic requirement was defined as the minimum anesthetic concentration (MAC) that prevented 50% animals from moving in response to a supramaximal stimulus. Levodopa (L-DOPA) dose-dependently decreased halothane MAC to a maximum of 49% of control; over the same dose range L-DOPA increased striatal dopamine nearly 4-fold. The MAC-reducing effect of L-DOPA was attenuated by selective antagonism of the D2 dopamine receptor with YM-09151-2 while selective blockade of the D1 dopamine receptor with SCH-23390 did not alter L-DOPA's effect on the MAC for halothane. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) decreased striatal dopamine by 82% and increased the MAC for halothane by 27%. Repletion of striatal dopamine with L-DOPA, in MPTP-treated mice, restored the MAC for halothane back to the control state. The regression line derived from the plot of halothane MAC versus striatal dopamine content shows a highly significant correlation between the two variables (r2 = 0.94). These are the first results to suggest that anesthetic requirements can be modulated directly and precisely by increasing or decreasing the content of a single neurotransmitter in the central nervous system.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1990

Pertussis toxin and 4-aminopyridine differentially affect the hypnotic-anesthetic action of dexmedetomidine and pentobarbital.

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. Pertussis toxin and 4-aminopyridine both decreased the hypnotic-anesthetic action of dexmedetomidine in a dose-dependent fashion. To preclude the possibility that pertussis toxin and 4-aminopyridine attenuated the hypnotic-anesthetic action of dexmedetomidine via indirect central nervous system excitation, the effects of pertussis toxin and 4-aminopyridine on the hypnotic-anesthetic action of pentobarbital also were assessed. Pentobarbital-induced hypnosis was not attenuated by either treatment. These results suggest that the receptor-effector mechanism for the hypnotic-anesthetic action of dexmedetomidine involves an inhibitory G-protein and increased conductance through a potassium channel.

4-Aminopyridine↗
PubMed1989

Dexmedetomidine produces a hypnotic-anesthetic action in rats via activation of central alpha-2 adrenoceptors.

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. Alpha-2 adrenoceptor antagonists that cross the blood-brain barrier (antipamezole and idazoxan) decreased the hypnotic-anesthetic action of dexmedetomidine in a dose-dependent fashion. In contrast, the alpha-2 antagonist, L-659,066, which does not penetrate into the CNS did not affect dexmedetomidine-induced hypnosis. Antagonists for the other adrenoceptors not only failed to reduce the hypnotic-anesthetic action of dexmedetomidine but in some cases even potentiated this effect. Thus, prazosin, an alpha-1 adrenoceptor antagonist, significantly enhanced the hypnotic-anesthetic property of dexmedetomidine. Antagonists with beta-2 receptor blocking properties also enhanced dexmedetomidine-induced hypnosis. Selective beta-1 receptor antagonists did not affect the hypnotic action of dexmedetomidine. These results suggest that dexmedetomidine produces a hypnotic-anesthetic action in rats via activation of central alpha-2 adrenoceptors.

Adrenergic alpha-Agonists↗
PubMed1989

Dexmedetomidine, acting through central alpha-2 adrenoceptors, prevents opiate-induced muscle rigidity in the rat.

The highly-selective alpha-2 adrenergic agonist dexmedetomidine (D-MED) is capable of inducing muscle flaccidity and anesthesia in rats and dogs. Intense generalized muscle rigidity is an undesirable side effect of potent opiate agonists. Although the neurochemistry of opiate-induced rigidity has yet to be fully elucidated, recent work suggests a role for a central adrenergic mechanism. In the present study, the authors determined if treatment with D-MED prevents the muscle rigidity caused by high-dose alfentanil anesthesia in the rat. Animals (n = 42) were treated intraperitoneally with one of the following six regimens: 1) L-MED (the inactive L-isomer of medetomidine), 30 micrograms/kg; 2) D-MED, 10 micrograms/kg; 3) D-MED, 30 micrograms/kg; 4) D-MED [30 micrograms/kg] and the central-acting alpha-2 antagonist, idazoxan [10 mg/kg]; 5) D-MED [30 micrograms/kg] and the peripheral-acting alpha-2 antagonist DG-5128 [10 mg/kg], or; 6) saline. Baseline electromyographic activity was recorded from the gastrocnemius muscle before and after drug treatment. Each rat was then injected with alfentanil (ALF, 0.5 mg/kg sc). ALF injection resulted in a marked increase in hindlimb EMG activity in the L-MED treatment group which was indistinguishable from that seen in animals treated with saline. In contrast, D-MED prevented alfentanil-induced muscle rigidity in a dose-dependent fashion. The small EMG values obtained in the high-dose D-MED group were comparable with those recorded in earlier studies from control animals not given any opiate. The high-dose D-MED animals were flaccid, akinetic, and lacked a startle response during the entire experimental period.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists↗
PubMed1989

Dexmedetomidine decreases halothane anesthetic requirements in rats.

alpha 2-Adrenergic agonists, such as clonidine, reduce the dose requirements for halothane. Medetomidine is more selective as a full agonist for central alpha 2-adrenoceptors than clonidine and is available as both an active (d) and an inactive (l) isomer. We have used the d-isomer to probe the mediating mechanism for the MAC-sparing effect of this alpha 2-agonist in rats. The dose of halothane which rendered 50% of animals insensitive to a painful stimulus (halothane MAC) was determined in rats (150-200 g) before and after d- or l-medetomidine, 10, 30 and 100 micrograms/kg or saline i.p. To determine whether alpha 2-adrenoreceptors mediated the MAC-sparing effect of dexmedetomidine (d-medetomidine), cohorts of rats (n = 6 for each dose) were pretreated with idazoxan, 10 mg/kg i.p., the highly selective alpha 2-antagonist. To determine whether dexmedetomidine's MAC-reducing action was mediated in part through either opiate or adenosine receptors, groups of rats were pretreated with either naltrexone, 5 mg/kg i.p., an opiate antagonist; or 8-phenyltheophylline (8-PT), 2.5 mg/kg i.p., an A1 adenosine antagonist. To determine whether postsynaptic mechanisms mediate the anesthetic-sparing effect of dexmedetomidine, rats were depleted of central norepinephrine stores with 6-OHDA and 4 days later MAC was determined before and after each dose of dexmedetomidine. Dexmedetomidine dose-dependently decreased MAC for halothane such that at the highest dose, halothane could be discontinued for up to 30 min without eliciting a response to tail-clamping. Idazoxan completely prevented the MAC-reducing action of dexmedetomidine, while naltrexone and 8-PT were without effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Anesthesia↗
PubMed1989

Pharmacologic characterization of the receptor mediating the hypnotic action of dexmedetomidine.

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. The centrally-active alpha 2-receptor antagonists, atipamezole (MPV-1248) and idazoxan, dose-dependently decreased the hypnotic action of dexmedetomidine. The peripherally-active alpha 2-receptor antagonist, DG-5128, did not reduce dexmedetomidine-induced hypnosis. The stereospecificity of dexmedetomidine's hypnotic action and its dose-dependent attenuation by alpha 2-antagonists confirmed the involvement of alpha 2-receptors in this effect. The finding that only alpha 2-antagonists with central activity attenuate the hypnotic action of dexmedetomidine, suggests that the mediating alpha 2-receptor is located in the central nervous system. In summary, this study suggests that dexmedetomidine induces hypnosis in rats by activating central alpha 2-adrenergic receptors. This study also suggests that alpha 2-antagonists can be used to reverse the hypnotic effects of dexmedetomidine.

Adrenergic alpha-Agonists↗
PubMed1989

Action of the stereoisomers of medetomidine, in halothane-anesthetized dogs.

This study was designed to investigate the anesthetic-reducing and cardiovascular effects of the stereoisomers of medetomidine in halothane-anesthetized male beagles. Anesthesia was induced by mask inhalation of halothane in oxygen, followed by 2h equilibration period. The minimum alveolar anesthetic concentration of halothane which prevented the animals from moving in response to a painful stimulus (MAC of halothane) was determined and baseline hemodynamic function was assessed. Dl-Medetomidine, at 3 doses (1, 3 and 10 micrograms.kg-1) was administered via the right atrial port over 15 minutes while maintaining the dog at its individual MAC for halothane. Ten minutes later, hemodynamic parameters were reassessed. MAC determination was then repeated. In two separate sets of experiments, dogs (n = 5 each) were administered either the d- or the 1-enantiomer of medetomidine and the same procedure followed as described above. MAC for halothane significantly decreased following dl-medetomidine administration in a dose-dependent fashion. The d-isomer displayed similar MAC-reducing effects while the 1-isomer was without effect. Neither isomer changed the mean arterial pressure while only and d-isomer significantly decreased heart rate and cardiac output.

Adjuvants, Anesthesia↗