page_title: Etoxadrol
section_title: Pharmacodynamics
hierarchical_section_title: Etoxadrol / Pharmacodynamics
caption_attribution_description: English: Normal vs. etoxadrol-inhibited NMDA receptor transmission
context_page_description: Etoxadrol is a dissociative anaesthetic drug that has been found to be an NMDA antagonist and produce similar effects to PCP in animals. Etoxadrol, along with another related drug dexoxadrol, were developed as analgesics for use in humans, but development was discontinued in the late 1970s after patients reported side effects such as nightmares and hallucinations.
context_section_description: Etoxadrol is a non-competitive NMDA receptor antagonist. It binds with high affinity to the PCP binding site on the NMDA receptor (Kᵢ = 107 nM, determined by the displacement of radiolabeled TCP). Normally, the inactivated NMDA receptor possesses a magnesium (Mg²⁺) block in the channel, blocking the passage of cations. 
  When the neurotransmitter glutamate binds to the NMDA receptor, and the postsynaptic cell membrane is depolarized (from the postsynaptic cell being activated), the magnesium block in the NMDA receptor channel is displaced. Calcium (Ca²⁺) and sodium (Na⁺) can enter the cell via the open channel, while potassium (K⁺) can exit the cell. Etoxadrol antagonizes the NMDA receptor by binding to the PCP site, located just above the magnesium block in the ion channel. In the event that the magnesium block is displaced, etoxadrol blocks the NMDA receptor channel, preventing cations from entering or exiting the channel. This mechanism of action also applies to PCP, TCP, ketamine and dexoxadrol.
  Etoxadrol binding does not affect the binding affinity of other sites on the NMDA receptor, as found by binding studies showing the displacement of radiolabeled TCP by etoxadrol (TCP binding in the absence of etoxadrol: Kᵢ = 19.2 x 10⁻⁹ M, Bₘₐₓ = 1.36 pmol/mg protein; TCP binding in the presence of etoxadrol: Kᵢ = 21.7 x 10⁻⁹ M, Bₘₐₓ = .66 pmol/mg protein).
  Despite its anesthetic and analgesic effects, etoxadrol does not interact with benzodiazepine, muscarinic acetylcholine, or mu opioid receptors.  However, etoxadrol may act in the dopamine reward pathway, explaining its reinforcing properties.
caption: NMDA receptor action in the absence (left) or presence (right) of etoxadrol.
exif: {}