Metabolism

Multistep Metabolism of 2-FDCK.[3] The process starts at 2-FDCK itself, which is then converted to nor-2-FDCK. This compound can then undergo transformation to either dehydro-nor-2-FDCK or hydroxy-nor-2-FDCK  

The metabolism of 2-FDCK is analogous to that of ketamine: the enzymes CYP2B6 and CYP3A4, the latter to a lesser extent, metabolise 2-FDCK to Nor-2FDCK via N-demethylation. This is further metabolised either to dehydronor-2FDCK by CYP2B6 or to hydroxynor-2FDCK by CYP2A6 and CYP2B6.[3] 

In general, the 2-FDCK equivalent shows stronger docking to CYP2B6 in simulations, as well as slower metabolism rate, than the more well-known Ketamine. The lipophilicity is observed to be lower for 2-FDCK than for Ketamine.[3] In vitro to in vivo extrapolation (IVIVE) predicts that in the body, 2-FDCK shows a lower intrinsic hepatic clearance than ketamine. Both of these characteristics would suggest that the effects of 2-FDCK last longer than those of ketamine

Pharmacodynamics

2-FDCK is structurally similar to ketamine, so a similar mechanism of action is expected,[9] but there has been no study done to confirm this. Due to the halogen in the 2 position not being a chlorine but a fluorine, the molecule is less polar.[3] This could influence binding to proteins, such as the NMDA receptor that ketamine primarily binds to and acts as an antagonist towards.

Comparison to other halogen-substituted ketamine variants

For general (halogen) substitutions of ketamine, docking strength for CYP2B6 follows the pattern H < Br < Cl < F. The parameter of internal clearance follows the pattern Br > Cl > F > H. Lastly, Km (Michaelis constant) follows the pattern of Br < Cl < F < H, and as such the in-vitro metabolism rate follows the inverse pattern, namely Br > Cl > F > H.

Dosage

2-FDCK is very new and not yet sufficiently studied. Therefore information on dosage can only be obtained from purely anecdotal sources.

Possible effects and dangers

In 2019, 2-FDCK was found in poisoned individuals in Hong Kong in combination with other ketamine-type drugs.[4] 2-FDCK was not assumed to be an impurity because it was present in high levels while ketamine was present at trace levels. The actual drug specimens were not available, so it was not possible to verify this. Clinical effects were observed but because the drug was taken in combination with other ones, it was not possible to determine what effects were caused by which drug. The clinically observed effects of the patients were: impaired consciousness, agitation, abnormal behaviour, hypertension and tachycardia. Most patients were discharged from the hospital after a few days of supportive treatment.