Orphenadrine  (Synonyms: (±)-Orphenadrine)

Orphenadrine ((±)-Orphenadrine) is a skeletal muscle relaxant and NMDA antagonist that also has antiparkinsonian, antihistamine, antitremor, antispasmodic, and analgesic effects. Orphenadrine inhibits the binding of ^[3H]MK-801 to the phencyclidine (PCP) binding site of the NMDA receptor. Orphenadrine is also an anticholinergic and cytochrome P450 (CYP) 2B inducer. Orphenadrine may exert pro-tumor effects, causing CAR nuclear translocation, resulting in microsomal reactive oxygen species (ROS) production and oxidative stress. Orphenadrine also exerts neuronal protection, protecting rat cerebellar granule cells (CGC) from 3-NPA-induced death and has inhibitory potential against neurodegenerative diseases mediated by NMDA receptor overactivation^[1][2][3].

NMDA receptor^[1]; CYP450 2B^[2]; Cholinesterase (ChE)^[3]

Orphenadrine (30-300 μM) exhibits relatively fast concentration-dependent open channel blocking kinetics with a K_off of 0.013^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

In a study of the tumor-promoting effects of Orphenadrine, male rats were pretreated with a single intraperitoneal injection of N-diethylnitrosamine (DEN) for 2 weeks. Orphenadrine (0, 750, 1500 ppm; po; 6 wk) accelerates hepatocyte proliferation and induces liver tumor-promoting activity^[2].
Orphenadrine (30 mg/kg; po; 3 d) Yes Protect rats from exposure to 3-nitropropionic acid (3-NPA) (30 mg/kg; 3 d), which causes neuronal damage in astrocytes. Markers: [(3)H]-PK 11195 and Increased expression levels of HSP27^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

269.38

C₁₈H₂₃NO

83-98-7

Solid

CN(C)CCOC(C1=C(C)C=CC=C1)C2=CC=CC=C2

Room temperature in continental US; may vary elsewhere.

• [1]. Kornhuber J, et al. Orphenadrine is an uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist: binding and patch clamp studies. J Neural Transm Gen Sect. 1995;102(3):237-46.  [Content Brief]

  [2]. Morita R, et al. Liver tumor promoting effect of orphenadrine in rats and its possible mechanism of action including CAR activation and oxidative stress. J Toxicol Sci. 2013;38(3):403-13.  [Content Brief]

  [3]. Pubill D, et al. Orphenadrine prevents 3-nitropropionic acid-induced neurotoxicity in vitro and in vivo. Br J Pharmacol. 2001 Feb;132(3):693-702.  [Content Brief]