HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

The analgesic activity of a clonidine analog. The formamidine, U-47,476A.

Abstract
A compound structurally related to clonidine, N,N-dimethyl-N'-(2,4, 6-trimethyl phenyl)formamidine hydrochloride (U-47,476A), was evaluated for analgesic activity; it produced a significant analgesia in mice and rats in several analgesiometric procedures. The analgesic potency varied considerably with different analgesiometric tests, with ED50s ranging from 0.4 mg/kg for writhing in mice induced by hydrochloric acid to greater than 30 mg/kg for the tail-flick test in rats. Although the potency was less than that of clonidine, it was still in the range of pentazocine. Then U-47,476A was further examined to determine whether the analgesic effect was mediated by alpha-adrenergic mechanisms and accompanied by hypotension and sedation, similar to that produced by clonidine. The drug U-47,476A failed to lower significantly blood pressure in rats given 10 and 30 mg/kg subcutaneously, suggesting a possible separation of the hypotensive and analgesic properties of this compound. The locomotor activity of mice was unaltered after 0.5 mg/kg of U-47,476A; however, a significant decrease in activity was observed after the administration of 5 mg/kg. The effect of U-47,476A on locomotor activity in the mouse was significantly less than that for an approximately equipotent analgesic dose of clonidine. The analgesic effect of U-47,476A was antagonized by yohimbine, but not by reserpine, naloxone or phentolamine, Thus, the attenuation of the response to noxious stimuli by U-47,476A is mediated by alpha 2-adrenoceptors and not by opioid receptors or presynaptic monoaminergic mechanisms, similar to clonidine-induced analgesia.
AuthorsJ S Mohrland, P F Von Voigtlander
JournalNeuropharmacology (Neuropharmacology) Vol. 24 Issue 12 Pg. 1207-10 (Dec 1985) ISSN: 0028-3908 [Print] England
PMID4094657 (Publication Type: Journal Article)
Chemical References
  • Amidines
  • Analgesics
  • Antihypertensive Agents
  • Hypnotics and Sedatives
  • Yohimbine
  • U 47476
  • Naloxone
  • Reserpine
  • Clonidine
  • Phentolamine
Topics
  • Amidines (pharmacology)
  • Analgesics
  • Animals
  • Antihypertensive Agents
  • Blood Pressure (drug effects)
  • Clonidine (analogs & derivatives)
  • Hypnotics and Sedatives
  • Mice
  • Motor Activity (drug effects)
  • Naloxone (pharmacology)
  • Phentolamine (pharmacology)
  • Rats
  • Rats, Inbred Strains
  • Reaction Time (drug effects)
  • Reserpine (pharmacology)
  • Species Specificity
  • Time Factors
  • Yohimbine (pharmacology)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: