title: Effect of ICI197067, a kappa-opioid receptor agonist, spinally on A delta and C reflexes and intracerebrally on respiration.
abstract: Intrathecal (i.t.) injection of a kappa-opioid receptor agonist, ICI197067, caused a similar dose dependent depression of A delta and C fibre mediated nociceptive reflexes in renal sympathetic nerves due to supramaximal electrical stimulation of tibial nerves in anaesthetized dogs. A total dose of 8 mg i.t. abolished these reflexes. When administered into the 4th ventricle (i.c.v.) in a total dose range from 0.1-2.5 mg ICI197067 caused no respiratory depression; a total dose of 10 mg i.c.v. abolished both phrenic nerve activity and spontaneous respiration. The ED50 ratio of ICI197067 for depression of respiration (i.c.v.) and somatosympathetic reflexes (i.t.) is approximately 1.5:1 compared with 0.3:1 for fentanyl. ICI197067 i.c.v. caused a similar reduction in arterial pressure compare to fentanyl without comparable changes in heart rate. Thus in terms of cardiorespiratory depression and blockade of A delta and C fibre pathways kappa-opioid receptor agonists may be safer and more effective for producing spinal analgesia than mu-opioid receptor agonists.
authors.affiliation: Department of Anaesthesia, Hammersmith Hospital, Royal Postgraduate Medical School, London, UK.
authors.forename: C
authors.initials: C
authors.lastname: Wang
authors.forename: M K
authors.initials: MK
authors.lastname: Chakrabarti
authors.forename: J G
authors.initials: JG
authors.lastname: Whitwam
mesh_terms: D000818:Animals; D017776:Autonomic Pathways / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D004558:Electric Stimulation; D005283:Fentanyl / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D007668:Kidney / Q000294:innervation / Q000502:physiology; D009294:Narcotics / Q000008:administration & dosage / Q000494:pharmacology*; D009412:Nerve Fibers / Q000187:drug effects* / Q000502:physiology; D009413:Nerve Fibers, Myelinated / Q000187:drug effects* / Q000502:physiology; D010791:Phrenic Nerve / Q000187:drug effects / Q000502:physiology; D011759:Pyrrolidines / Q000008:administration & dosage / Q000494:pharmacology*; D017473:Receptors, Opioid, kappa / Q000187:drug effects*; D012018:Reflex / Q000187:drug effects* / Q000502:physiology; D012119:Respiration / Q000187:drug effects*; D013564:Sympathetic Nervous System / Q000166:cytology / Q000187:drug effects / Q000502:physiology
chemical_list: D009294:Narcotics; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; C058467:ICI 197067; D005283:Fentanyl