Pharmacological studies of 1-(2,3-dimethyl-4-methoxyphenyl)-2-methyl-3-(1-pyrrolidinyl)-1- propanone hydrochloride (AD-2239), a centrally acting muscle relaxant.

Abstract

Centrally acting muscle relaxant properties of AD-2239 were compared with those of tolperisone, eperisone, diazepam and baclofen. AD-2239 dose-relatedly depressed extensor reflex in urethane-chloralose anesthetized intact and spinal rats, the i.v. potencies being similar to those of tolperisone and eperisone. These effects of AD-2239 were long-lasting. When orally administered, AD-2239 was 4 times more potent than eperisone. Diazepam was without effect on the extensor reflex in spinal rats. AD-2239 depressed the flexor reflex without affecting the patellar reflex in anesthetized cats. Baclofen depressed the latter. When orally administered, AD-2239, in a dose-related manner, depressed the flexor reflex in anesthetized cats, with a potency approximately 8 times that of tolperisone or eperisone. AD-2239 produced a dose-related reduction of anemic decerebrate rigidity (alpha-rigidity) in rats. The potency, at the minimum effective i.v. dose, was 4 times greater than that of tolperisone or eperisone, equal to that of diazepam, and one-half of that of baclofen. AD-2239 neither affected spontaneous electroencephalogram (EEG) nor EEG arousal response in immobilized cats, while the other drugs, at comparatively low doses, depressed them. The results strongly suggest that AD-2239 may have advantages over the existing centrally acting muscle relaxants in the treatment of human clinical spasticity and muscle spasm syndromes.

• Authors: T Ito, M Hori, K Furukawa, T Karasawa, T Kadokawa
• Journal: Archives internationales de pharmacodynamie et de therapie (Arch Int Pharmacodyn Ther) Vol. 275 Issue 1 Pg. 105-22 (May 1985) ISSN: 0003-9780 [Print] Belgium
• PMID: 3839647 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Muscle Relaxants, Central
• Propiophenones
• Pyrrolidines
• eperisone
• AD 2239
• Tolperisone
• Baclofen
• Diazepam

Topics

• Animals
• Arousal (drug effects)
• Baclofen (pharmacology)
• Behavior, Animal (drug effects)
• Cats
• Decerebrate State
• Diazepam (pharmacology)
• Electroencephalography
• Electromyography
• Female
• Macaca mulatta
• Male
• Mice
• Mice, Inbred Strains
• Muscle Relaxants, Central (pharmacology)
• Muscle Rigidity (prevention & control)
• Propiophenones (pharmacology)
• Pyrrolidines (pharmacology)
• Rats
• Rats, Inbred Strains
• Reflex (drug effects)
• Reflex, Stretch (drug effects)
• Species Specificity
• Tolperisone (pharmacology)