Misc NDMA Atagonist Effect from 100MG Oprhendrine Tablets Sold OTC in Canada as Orfenace.

[Thomas29]

So I just Read on Wikipedia that Orphenadrine has NMDA Atagonist Effect And from Research And PERSONAL Experience the strong CYP2B6 Inhibition not only makes SPECIFICALLY Hydromorphone Pain-Relief And STRONGER INCLUDING LONGER Methadone is the most Strongly Effected it produces more R-Methadone And the good effects of Methadone Plus it By the Strong CYP2B6 Inhibition it also Inhibits CYP3A4 And CYP2D6 Strongly.


So the question is HOW STONGLY is the NMDA Atagonist Effect that Orphenadrine produces? If it has an NMDA Atagonist Effect at all since I LITERALLY just Read that on Wikipedia ROFL! So...

 

[Jekyl Anhydride]

Orphenadrine:
(Ki-value of 6.0 +/- 0.7 μM, one third as potent as phencyclidine, which binds with a Ki of 2 μM)

Interesting but not exactly groundbreaking.
https://www.ncbi.nlm.nih.gov/pubmed/8788072

I'm more of a fan of Memantine or even DXM
https://www.ncbi.nlm.nih.gov/pubmed/8152525

Or the true NMDA gems..
https://www.ncbi.nlm.nih.gov/pubmed/12232776

 

[Thomas29]

Well the point of Orphenadrine is it STRONGLY Inhibits CYP2B6 Great for Hydromorphone in pain relief trials and known liver Enzyme Metabolizer for Methadone But it is A Strong CYP2D6 Inhibitor And A Partial CYP3A4 Enzyme Inhibitor

 

[d1nach]

Wouldnt you experiance also anticholinergic side effects ?

 

[Speed King]

I have 100 mg tablets of ophenadrine. YMMV, but the diphenhydramine comparison is right. It is suppose to be 1/3 strength of phencyclidine.

As far as the anticholinergic go, I now remember taking at least a 200 mg dose. It had anticholinergic effects but were less pronounced then diphenhydramine Mg for Mg, IMO. I definately wouldn't jump straight to a >100mg dose.

 

[d1nach]

Isnt pcp dosed at 3-10 mg if its 1/3 the potency of pcp why doesnt 100 mg produce full blown anesthesia ? Can someone elaborate because i dont get it.

 

[Jekyl Anhydride]

PCP is an Arylcyclohexylamine dissociative whereas Orphenadrine is an antihistamine very similar to diphenhydramine. While both have NMDAr antagonist properties that's not the only factor to their differing effects as each is in an entirely different class of drug. These abstracts below might elucidate it better than myself.

https://www.ncbi.nlm.nih.gov/pubmed/12232776

Thus, ketamine and PCP may not produce a selective hypoglutamate state, but more likely produce a non-selective multi-system neurochemical perturbation via direct and indirect effects.

https://www.ncbi.nlm.nih.gov/pubmed/7968938

Phencyclidine (PCP), a psychotomimetic drug with anticonvulsant and neuroprotective properties interacts with several central nervous system (CNS) macromolecules. These include cholinergic receptors, potassium channels, biogenic amine reuptake systems, the N-methyl-D-aspartate (NMDA) excitatory amino acid receptor, and sigma binding sites. The good correlation between the affinity of arylcycloalkylamines for high affinity PCP binding sites and their ED50 values for inhibition of [3H]dopamine uptake supports the notion that a PCP binding site associated with the transporter for the biogenic amines should be detectable in ligand binding studies. This article reviews data primarily from the author's laboratory, which shows that the PCP analog, [3H]1-[1-(2-thienyl)cyclohexyl]piperidine, binds to a second site, not associated with the NMDA receptor/ionophore complex, called PCP site 2. The ligand-selectivity of this binding site and the evidence that it is associated with the biogenic amine transporters are reviewed.

https://www.ncbi.nlm.nih.gov/pubmed/2557536

Taken collectively, these data demonstrate the existence of a high affinity PCP binding site associated with the dopamine reuptake carrier and raise the possibility that the therapeutic and psychotomimetic effects of PCP in humans are separable and mediated via different binding sites.

Phencyclidine = IC50 = 0.821 uM

Orphenadrine=The IC50-value against steady state currents at -70 mV was 16.2 +/- 1.6 microM



Effects of Ketamine on non NMDA & opioid sites
https://www.ncbi.nlm.nih.gov/pubmed/7840409

 

[Speed King]

I did read what I posted, possibly out of context. The lower the number, the more potent. In that regard, the difference is rougly 20 x in the above post.

Until I get to explore deeper, Ketamine FTW!

DXM is passable, but sub par on its own. It complements Ketamine after an infusion.

 

[d1nach]

Interesting info jekyll