Cats (n = 6) were administered dexmedetomidine (DEX) and medetomidine (MED) at three different dose levels in a randomized, blinded, cross-over study. DEX was administered at 25, 50 and 75 microg/kg (D25, D50 and D75), corresponding to MED 50, 100 and 150 microg/kg (M50, M100 and M150). Sedation, analgesia and muscular relaxation were scored subjectively. Heart and respiratory rates and rectal temperature were measured. Corresponding doses of DEX and MED were compared. Effects were also compared between dose levels for each compound. At dose level 2 (D50-M100), the duration of effective clinical sedation was significantly shorter after DEX (202.5 +/- 16.0 min) than after MED (230.0 +/- 41.2 min). Proceeding from D50-M100 to D75-M150, the duration of effective clinical sedation was increased more after DEX (by 57.5 +/- 38.4 min) than after MED (by 14.2 +/- 41.9 min) Increasing from D50-M100 to D75-M150, heart rate was further decreased after DEX (by 8.1 +/- 13.4%) but not after MED. There was no statistically significant difference between corresponding doses of DEX and MED for any of the other parameters studied. Changes in sedation, analgesia and muscular relaxation were dose-dependent. It was concluded that anaesthetic effects of medetomidine in cats are probably due entirely to its d-isomer and that dexmedetomidine at 25, 50 and 75 microg/kg induces dose-dependent sedation, analgesia and muscular relaxation of clinical significance in cats.

Dexmedetomidine (DEX) may have some therapeutic advantages over the racemate medetomidine (MED). Here we have examined how serum concentrations of DEX correlate with some of its anaesthetic effects. Cats (n = 6) were administered with a continuous stepwise intravenous (i.v.) infusion of DEX or MED on different occasions in a cross-over design. Maintenance infusion rates (mg/kg/min) used were: DEX = 0.25 (MED = 0.50); DEX = 1 (MED = 2) and DEX = 4 (MED = 8) for infusion steps 1, 2 and 3, respectively. Each maintenance infusion lasted at least 50 min and was preceded with a loading dose. There was no significant difference between serum DEX and 0.5 serum MED concentrations at any dose level nor was there a significant difference between serum DEX and the (entire) serum MED concentrations. There was no significant difference between DEX and MED for sedation, analgesia, muscular relaxation and heart and respiratory rates. For both DEX and MED, serum drug concentration and analgesia were dose-dependent and sedation increased until the end of infusion step 2 (dose level 2) and decreased at the end of step 3 (dose level 3). Muscular relaxation was not dose-dependent. We conclude that increasing the blood concentration of DEX or MED beyond a certain level decreases the level of sedation instead of increasing it even though analgesia increases. The rate at which DEX and MED are metabolized in cats may not be the same.

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Earlier studies indicate that striatal dopamine D(2) receptors are involved in pain regulation in non-neuropathic conditions. We assessed whether striatal dopamine D(2) receptors contribute to pain regulation also in neuropathic conditions. The spared nerve injury model of neuropathy was induced by unilateral ligation of the tibial and common peroneal nerves in the rat. In awake nerve-injured animals, pain-related withdrawal responses to calibrated monofilaments or noxious heating were attenuated following striatal administration of a dopamine D(2) receptor agonist quinpirole. Pain-related responses were attenuated only in the nerve-injured limb ipsilateral to the injection and in the midline (tail). In unoperated controls, striatal administration of quinpirole at an antihypersensitive dose did not influence withdrawal responses to mechanical stimulation. Attenuation of pain-related responses induced by striatal administration of quinpirole was reversed by intrathecal administration of a dopamine D(2) receptor antagonist (eticlopride) or a non-selective 5-HT receptor antagonist (methysergide), but not by an alpha(2)-adrenoceptor antagonist (atipamezole). In the rostroventromedial medulla of lightly anesthetized neuropathic animals, striatal administration of quinpirole significantly decreased the activity of presumably pronociceptive cells that are activated by noxious stimulation. The innocuous H-reflex in lightly anesthetized control animals was not suppressed by striatal administration of quinpirole at an antihypersensitive dose. The results indicate that striatal dopamine D(2) receptors attenuate neuropathic hypersensitivity. The antihypersensitive effect induced by striatal dopamine D(2) receptors in peripheral neuropathy involves suppression of impulse discharge of presumably pronociceptive neurons in the rostroventromedial medulla, and a descending influence acting on spinal 5-HT and dopamine D(2) receptors.