title: Imidazoline I(2)-receptors and spinal reflexes in the decerebrated rabbit.
abstract: Idazoxan potentiates spinal reflexes in the decerebrated rabbit, an effect that has been attributed to antagonism of tonic noradrenergic inhibition. It is now known that this drug has a higher affinity for I(2)-imidazoline receptors than alpha(2)-receptors. The roles of I(2)-receptors in modulating transmission in spinal reflex pathways have been investigated using the selective ligands RX 821029 and RS-45041-190, and, as I(2)-receptors are closely associated with monoamine oxidase (MAO), the MAO inhibitors pargyline and clorgyline. In decerebrated rabbits with an intact spinal cord, intrathecal doses of 5-365 microg (cumulative) of the I(2)-ligands augmented, to 150-180% of pre-drug levels, the reflex responses of medial gastrocnemius motoneurones to electrical stimulation of the sural nerve, and significantly increased mean arterial blood pressure by approximately 10 mmHg over pre-drug values. Neither MAO inhibitor had significant effects on reflexes, but the highest dose of the MAO-A selective agent clorgyline (365 microg cumulative) caused a significant rise in blood pressure of 6 mmHg. Neither the I(2)-ligands nor the MAO inhibitors prevented the further enhancement of reflexes or blood pressure by subsequent administration of the selective alpha(2)-adrenoceptor antagonist RX 821002. In decerebrated, spinalized rabbits, intrathecal RS-45041-190 (60 microg, single dose) increased spinal reflex responses to 109% of pre-drug values, a significantly smaller effect than that seen in non-spinal preparations, and had no effect on blood pressure. These data show that imidazoline I(2)-receptors can influence somatic and autonomic motor outflows. These effects should be taken into account when interpreting the spinal effects of imidazoline-based adrenoceptor-active drugs.
authors.affiliation: Division of Animal Physiology, School of Biological Sciences, University of Nottingham, Sutton Bonington Campus, Leics, LE12 5RD, Loughborough, UK. robert.clarke@nottingham.ac.uk
authors.forename: R W
authors.initials: RW
authors.lastname: Clarke
authors.forename: J
authors.initials: J
authors.lastname: Harris
authors.forename: J
authors.initials: J
authors.lastname: Ogilvie
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003010:Clorgyline / Q000494:pharmacology; D003655:Decerebrate State; D004305:Dose-Response Relationship, Drug; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D019329:Idazoxan / Q000031:analogs & derivatives / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D054755:Imidazoline Receptors; D007211:Indoles / Q000494:pharmacology; D007278:Injections, Spinal; D054833:Isoindoles; D008024:Ligands; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D010293:Pargyline / Q000494:pharmacology; D011817:Rabbits; D011955:Receptors, Drug / Q000502:physiology*; D012018:Reflex / Q000187:drug effects / Q000502:physiology*; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*
chemical_list: D000317:Adrenergic alpha-Antagonists; D007093:Imidazoles; D054755:Imidazoline Receptors; D007211:Indoles; D054833:Isoindoles; D008024:Ligands; D008996:Monoamine Oxidase Inhibitors; D011955:Receptors, Drug; C097364:4-chloro-2-(imidazolin-2-yl)isoindoline; D010293:Pargyline; C058525:2-methoxyidazoxan; D003010:Clorgyline; D019329:Idazoxan