Document Detail


Antinociceptive and hemodynamic effects of a novel alpha2-adrenergic agonist, MPV-2426, in sheep.
MedLine Citation:
PMID:  10551595     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: alpha2-Adrenergic agonists produce analgesia primarily by a spinal action and hypotension and bradycardia by actions at several sites. Clonidine is approved for epidural use in the treatment of neuropathic pain, but its wider application is limited by hemodynamic side effects. This study determined the antinociceptive and hemodynamic effects of a novel alpha2-adrenergic agonist, MPV-2426, in sheep. METHODS: Forty sheep of mixed Western breeds with indwelling catheters were studied. In separate studies, antinociception to a mechanical stimulus, hemodynamic effects, arterial blood gas tensions, cerebrospinal fluid pharmacokinetics, and spinal cord blood flow was determined after epidural, intrathecal, and intravenous injection of MPV-2426. RESULTS: MPV-2426 produced antinociception with greater potency intrathecally (ED50 = 49 microg) than epidurally (ED50 = 202 microg), whereas intravenous administration had no effect. Intrathecal injection, in doses up to three times the ED95, failed to decrease systemic or central arterial blood pressures or heart rate, whereas larger doses, regardless of route, increased systemic arterial pressure. Bioavailability in cerebrospinal fluid was 7% after epidural administration and 0.17% after intravenous administration. Intrathecal MPV-2426, in an ED95 dose and three times this dose, produced a dose-independent reduction in thoracic and lumbar spinal cord blood flow. CONCLUSIONS: MPV-2426 shares many characteristics of other alpha2-adrenergic agonists examined in sheep, but differs from clonidine and dexmedetomidine by lack of antinociception and minimal reduction in oxygen partial pressure after large intravenous and epidural injections. No hemodynamic depression was observed after intrathecal injection at antinociceptive doses. These results suggest this compound may be an effective spinal analgesic in humans with less hypotension than clonidine, although its relative potency to cause sedation was not tested in this study.
Authors:
J C Eisenach; P Lavand'homme; C Tong; J K Cheng; H L Pan; R Virtanen; H Nikkanen; R James
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Anesthesiology     Volume:  91     ISSN:  0003-3022     ISO Abbreviation:  Anesthesiology     Publication Date:  1999 Nov 
Date Detail:
Created Date:  1999-11-24     Completed Date:  1999-11-24     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  1300217     Medline TA:  Anesthesiology     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1425-36     Citation Subset:  AIM; IM    
Affiliation:
Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA. eisenach@wfubmc.edu
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MeSH Terms
Descriptor/Qualifier:
Adrenergic alpha-Agonists / cerebrospinal fluid,  pharmacokinetics,  pharmacology*
Algorithms
Analgesics / cerebrospinal fluid,  pharmacokinetics,  pharmacology*
Animals
Blood Gas Analysis
Female
Hemodynamics / drug effects*
Imidazoles / pharmacokinetics,  pharmacology*
Indans / pharmacokinetics,  pharmacology*
Injections, Spinal
Receptors, Adrenergic, alpha-2 / agonists*
Regional Blood Flow / drug effects
Sheep
Spinal Cord / blood supply,  drug effects
Chemical
Reg. No./Substance:
0/Adrenergic alpha-Agonists; 0/Analgesics; 0/Imidazoles; 0/Indans; 0/Receptors, Adrenergic, alpha-2; 0/radolmidine

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