Drugs acting at calcium channels can influence the hypnotic-anesthetic effect of dexmedetomidine.
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. Chronic treatment with verapamil (1 or 5 mg/kg) significantly increased the duration of the hypnotic-anesthetic effect of dexmedetomidine. Neither acute treatment with verapamil nor the calcium channel agonist BAY K 8644 (0.5 or 1 mg/kg) influenced the dexmedetomidine-induced hypnosis after DSP-4 treatment. The results seem to support the idea that the hypnotic action of dexmedetomidine can be affected via modulation of the transmembraneous calcium movement in the central nervous system. Further, the data on catecholamine-depleted rats with DSP-4 suggest that the interactions between verapamil and dexmedetomidine may be mediated through presynaptic or homoreceptors on noradrenergic neurons.
Department of Physiology, Albert Szent-Györgyi Medical University, Szeged, Hungary.
G
G
Horváth
M
M
Kovács
M
M
Szikszay
G
G
Benedek
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D001596:Benzylamines / Q000008:administration & dosage; D004357:Drug Synergism; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D020926:Medetomidine; D014179:Neurotransmitter Uptake Inhibitors / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D014700:Verapamil / Q000494:pharmacology*
D000316:Adrenergic alpha-Agonists; D000777:Anesthetics; D001596:Benzylamines; D006993:Hypnotics and Sedatives; D007093:Imidazoles; D014179:Neurotransmitter Uptake Inhibitors; D014700:Verapamil; D020926:Medetomidine; C012102:DSP 4