Clinical and Pharmacological Review of the Efficacy of Orphenadrine and Its Combination with Paracetamol in Painful Conditions

Abstract

Orphenadrine citrate, a monomethylated derivative of diphenhydramine, has been used as a muscle relaxant and as an analgesic both alone or as a constituent of combination products. Data on the efficacy of orphenadrine alone and in combination with paracetamol for painful conditions are evaluated in the present review. From the available animal data it is concluded that the antinociceptive effect of orphenadrine has been clearly demonstrated but data have also clearly indicated that it has muscle relaxant properties. Human placebo-controlled studies have shown some support for the view that orphenadrine on its own acts as a mild analgesic in painful conditions associated with muscle spasm. Although only a small number of well-controlled studies have been completed with the combination product of orphenadrine/paracetamol, each supports the view that the combination has superior efficacy over paracetamol alone. There is no doubt that the combination product is more efficacious than placebo.

Efficacy and safety of combined piroxicam, dexamethasone, orphenadrine, and cyanocobalamin treatment in mandibular molar surgery

“…Drugs that have muscle-relaxing activity combined with NSAIDs and analgesics may reduce muscle spasms after injurycausing procedures better than when used alone (29). The synergistic effect of the concomitant use of dexamethasone and piroxicam can lead to a reduction in the dose of orphenadrine since only a 35-mg dose is present in the Rheumazin formulation (30).…”

Reduction of Tinnitus Severity by the Centrally Acting Muscle Relaxant Cyclobenzaprine: An Open-Label Pilot Study

“…These compounds were chosen since either there exist no previous reports for their use in tinnitus (cyclobenzaprine and tizanidine) or just isolated cases (orphenadrine [Abdul-Baqi, 2004] and eperisone [Murai et al, 1992]) have been published. Moreover, they all have a central nervous system mechanism of action and have been used in the treatment of different forms of pain [Cabitza and Randelli, 2008;Chau et al, 1998;Desaphy et al, 2009;Hunskaar and Donnell, 1991;Ishizuki and Yanagisawa, 1992;Kino et al, 2005;Kobayashi et al, 1996;Kornhuber et al, 1995;Leite et al, 2009;Sayers et al, 1980;Yang et al, 2011], a disorder that has some striking pathophysiological similarities with tinnitus Moller, 2007b]. …”

Evaluation of the phencyclidine-like discriminative stimulus effects of novel NMDA channel blockers in rats

“…In vivo, alaproclate attenuates NMDAreceptor-mediated increases in cGMP and prevents NMDA-induced seizures in rats (Hu and Ross 1997). Orphenadrine, a derivative of the antihistamine diphenhydramine, is marketed for use as a muscle relaxant (Finch 1959;Hoddes 1964) and analgesic (Hunskaar and Donnell 1991) and has also been used for over 30 years in the symptomatic treatment of Parkinson's disease (Doshay and Constable 1957;Mindham et al 1972). Orphenadrine binds with low affinity to the NMDA channel and blocks NMDA-induced currents in a voltageand use-dependent manner (Kornhuber et al 1995).…”