MD-354 potentiates the antinociceptive effect of clonidine in the mouse tail-flick but not hot-plate assay.
Albeit conflicting, evidence suggests that 5-HT3 receptor partial agonists as well as alpha2NON-A-adrenoceptor agonists might be involved in antinociception. MD-354 (m-chlorophenylguanidine) can be viewed as the first example of a rather selective 5-HT3/alpha2B-adrenergic ligand. In a tail-flick test in mice, subcutaneous administration of MD-354 doses up to 30 mg/kg did not produce antinociception and failed to antagonize the effect of clonidine (ED50=0.5 mg/kg), but a combination of an inactive de of clonidine (0.25 mg/kg) that produced only 13% maximal possible effect (MPE) with an inactive dose of MD-354 (10 mg/kg, MPE=8%) produced an antinociceptive effect (MPE=83%). In the hot-plate assay, neither subcutaneous administration of MD-354 (3 to 30 mg/kg) alone nor in combination with clonidine (ED50=0.8 mg/kg) produced an antinociceptive effect. MD-354 was demonstrated to potentiate the antinociceptive effect of clonidine in the tail-flick assay, but its underlying mechanism remains to be determined.
Wesolowska
Anna
A
Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, Box 980540 VCU, Richmond VA 23298-0540, USA.
Young
Shawquia
S
Dukat
Malgorzata
M
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D001667:Binding, Competitive; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006146:Guanidines / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine / Q000494:pharmacology; D010146:Pain / Q000517:prevention & control; D010147:Pain Measurement / Q000379:methods*; D011869:Radioligand Assay; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism; D011985:Receptors, Serotonin / Q000378:metabolism
C547714:Adra1a protein, mouse; C547717:Adra1b protein, mouse; D000700:Analgesics; D001549:Benzamides; D019086:Bridged Bicyclo Compounds, Heterocyclic; D006146:Guanidines; D018340:Receptors, Adrenergic, alpha-1; D018341:Receptors, Adrenergic, alpha-2; D011985:Receptors, Serotonin; C495409:m-chlorophenylguanidine; C078730:serotonin 5 receptor; C104425:serotonin 7 receptor; D044282:Receptor, Serotonin, 5-HT1A; D009020:Morphine; C055971:zacopride; D003000:Clonidine