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Diphenidine (1-(1,2-diphenylethyl)piperidine) is a dissociative NMDA receptor antagonist and anesthetic drug that has been sold online as a research chemical.
The synthesis of diphenidine was first reported in 1924 and employed a nitrile displacement reaction analogous to the one that would later be used to discover phencyclidine in 1956. Anecdotal reports describe high doses of diphenidine producing “bizarre somatosensory phenomena and transient anterograde amnesia.” Based on collaborative anecdotal evidence, diphenidine seems to have a much more rapid onset and lower half life when vaporized or smoked. When consumed this way, it is a suspected to be carcinogenic when excess heat is used. Some user reports have concluded that vaporization requires as low as 20% of what would be a common oral dose for that person.
Diphenidine is a diarylethylamine related to methoxphenidine. It is named for its two phenyl and piperidine groups. Diphenidine ‘s crystalline structure is very similar to MK-801 (Dizocilpine) and shares many of the same effects. These two compounds are homeomorphs. Diphenidine is synthesized in a reaction analogous to the synthesis of PCP. The (R)-enantiomer of diphenidine has a remarkable high affinity as a NMDA receptor channel blocker.
Diphenidine acts as an NMDA receptor antagonist. NMDA receptors allow for electrical signals to pass between neurons in the brain and spinal column; for the signals to pass, the receptor must be open. NMDA receptor antagonists close the NMDA receptors by blocking them. This disconnection of neurons leads to loss of feeling, difficulty moving, and eventually the famous “hole”. Although vendors of diphenidine have stated the compound acts as a dopamine-reuptake inhibitor and a serotonin reuptake inhibitor with u-opioid affinity and typical dissociative effects, to date diphenidine has not been screened for affinity at the dopamine transporter. If this is indeed the case, however, it provides an explanation for its euphoric and often stimulating effects. Diphenidine and related diarylethylamines have been studied in vitro as treatments for neurotoxic injury. Diphenidine may be a stronger NMDA receptor antagonist for neurogenis and neurological repair than other more common NMDA receptor antagonistic dissociatives such as ketamine, dextromethorphan, PCP analogs, Iboga and methoxetamine.
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