Author Topic: 1-methylamino-1-(2-methylphenyl)cyclohexane  (Read 675 times)

0 Members and 1 Guest are viewing this topic.

neuromodulator

  • Guest
1-methylamino-1-(2-methylphenyl)cyclohexane
« on: April 17, 2002, 03:27:00 PM »
Has this compound ever been tested for psychoactivity?  All it is is ketamine with a methyl group replacing the chlorine.

PrimoPyro

  • Guest
Carbonyl
« Reply #1 on: April 17, 2002, 04:34:00 PM »
And missing the oxygen that creates the carbonyl on the cyclohexane ring.

Vivent Longtemps La Ruche!

terbium

  • Guest
PCP
« Reply #2 on: April 17, 2002, 08:59:00 PM »
Yes, it seems more like PCP than Ketamine.

Edit

Here is a mention of PCE which is 1-(N-ethylamino)-1-phenylcyclohexane :

https://www.thevespiary.org/rhodium/Rhodium/chemistry/pcp/pcp_struc.html


PrimoPyro

  • Guest
Good Info
« Reply #3 on: April 17, 2002, 09:13:00 PM »

hms_beagle

  • Guest
1-methylamino-1-(2-methylphenyl)cyclohexane
« Reply #4 on: April 21, 2002, 09:34:00 PM »

Has this compound ever been tested for psychoactivity?  All it is is ketamine with a methyl group replacing the chlorine.




Undoubtedly Parke Davis & Co. looked at it during Ketamine development. Unfortunately their data on  activity of analogs has never been published.

I'd be willing to bet that this compound is more active as a recreational drug than Ketamine though.


hms_beagle

  • Guest
Re: Unfortunately their data on activity of ...
« Reply #5 on: May 27, 2002, 01:50:00 PM »

Unfortunately their data on activity of analogs has never been published.




I came across a couple of refs that may mention this compound . I've only looked at their abstracts so far. The papers are not specifically geared towards psychoactivity, but may contain useful info about relative binding affinitys of different analogs. If anyone looks them up, let me know about anything interesting

***********************************************
Bibliographic Information

PCP receptor binding affinity predicts potency in inhibiting glutamate induced calcium accumulation in neuronal cell cultures.     Coughenour, L. L.; Brahce, L. J.; Courtland, G. G.; Johnson, G.; Malone, T.; Probert, A. W.; Marcoux, F. W.    Parke-Davis Pharm. Res. Div.,  Warner-Lambert Co.,  Ann Arbor,  MI,  USA.    Neurol. Neurobiol.  (1988),  46(Front. Excitatory Amino Acid Res.),  563-6.  CODEN: NEUND9  ISSN: 0736-4563.  Journal  written in English.    CAN 110:148421    AN 1989:148421    CAPLUS   (Copyright 2002 ACS) 

Abstract

Arylcyclohexylamine derivs. and other N-methyl-D-aspartate (NMDA) antagonists were evaluated for their affinity for the phencyclidine (PCP) receptor in rat brain membranes and for their potency in blocking 45Ca2+ accumulation in cerebral cortical neuron cultures stimulated by glutamate.  There was a close correlation between the potency to inhibit [3H]thienylcyclohexylpiperidine binding to brain membranes and the potency to block glutamate-induced 45Ca2+ accumulation by cultured cortical neurons.  These findings are consistent with previous data in that the affinity for the PCP site will predict the potency of the agent in producing a steric blockade of the cation channel assocd. with the NMDA subtype of the glutamate receptor.

Bibliographic Information

Local anesthetic properties of opioids and phencyclidines:  interaction with the voltage-dependent, batrachotoxin binding site in sodium channels.     Creveling, C. R.; McNeal, E. T.; Lewandowski, G. A.; Rafferty, M.; Harrison, E. H.; Jacobson, A. E.; Rice, K. C.; Daly, J. W.    Natl. Inst. Arthritis, Diabetes, Dig. Kidney Dis.,  NIH,  Bethesda,  MD,  USA.    Neuropeptides (Edinburgh)  (1985),  5(4-6),  353-6.  CODEN: NRPPDD  ISSN: 0143-4179.  Journal  written in English.    CAN 102:214975    AN 1985:214975    CAPLUS   (Copyright 2002 ACS) 

Abstract

3H-labeled batrachotoxinin A 20a-benzoate (BTX-B)  [78870-19-6] binds specifically and with high affinity to a site on voltage-dependent Na+ channels.  Compds. with local anesthetic activity inhibit the binding of [3H]BTX-B by a mutually exclusive, allosteric mechanism.  The potential local anesthetic potency of a series of 23 opioids and phencyclidine-like compds. was estd. by their inhibition of [3H]BTX-B binding to Na+ channels in a prepn. of synaptoneurosomes from guinea pig cerebral cortex.  The potency of these compds. as inhibitors of the specific binding of 3H-labeled phencyclidine (PCP)  [77-10-1] to a high-affinity site on rat brain membranes was also detd.  Opioids such as morphine  [57-27-2] and (-)-naloxone  [465-65-6] show little affinity for the [3H]BTX-B binding site or for the [3H]PCP binding site.  Other analgesics, many of the PCP-like compds., and dioxadrol derivs. are potent inhibitors of [3H]BTX-B binding and display both stereospecificity and high affinity towards the PCP-binding site.  However, there was no correlation between local anesthetic potency (assessed as antagonism of [3H]BTX-B binding) and affinity towards the PCP site.  Five classical local anesthetics had no affinity for the PCP site, but did displace [3H]BTX-B from its binding site.
******************************************************
 
A 2-methyl should be a favorable substitution in these compounds though. In JMC 1990 33, 1452-1458, the addition of a 2-methyl to  phenylcyclohexylamine increased its potency. It is interesting that ketamine has a 2-chloro, since this probably decreases binding affinity. The 2-chloro may enhance speed of penetration into the CNS though, which is a more important property in an anesthetic.

Its the 4-methyl compound that bothers me though. Several papers have suggested that it has lower potency in receptor binding assays. But I'd like to see a more personal approach to evaluating it.


Lilienthal

  • Guest
sigma-1
« Reply #6 on: May 27, 2002, 08:52:00 PM »
Isn't the really important binding site for PCP and  ketamine the sigma-1 receptor? The sigma-1 is a pretty interesting receptor BTW, completely unrelated to G-protein coupled receptors or ion channels. It's a receptor for neuroactive steroids.

I've heard that NMDA receptor antgonism makes you only drunken, pretty much like like from alcohol  :)

hms_beagle

  • Guest
sigma vs. NMDA
« Reply #7 on: May 28, 2002, 12:47:00 AM »
I'm not totally current on sigma subtypes, but it certainly is an interesting receptor that may have a role in psychoactivity. Ketamine and PCP bind to both sigma receptors and NMDA receptors (as noncompetitive antagonists).  The central effects are commonly thought to result from binding to NMDA . I don't believe that PCP has  much affinity for sigma sites.
************
Behav Brain Res 2001 Feb 15;119(1):33-40   
Phencyclidine-induced discriminative stimulus is mediated via phencyclidine binding sites on the N-methyl-D-aspartate receptor-ion channel complex, not via sigma(1) receptors.
*********************

Certain sigma-1 selective agonists reverse some of the behaviors used to evaluate PCP activity though, so maybe there is a role.

Sigma sites may account for some of the CNS effects of dextromethorhan and benzomorphans such as pentazocine. These compounds are said to have psychotropic activity that seems distict from other classes, although somewhat similar to PCP.

As far as these drugs causing a drunken state, I feel that it is a much more complex and rich intoxication. But there are many similarities too (like making you act like an idiot). I tend to mostly agree w/ Shulgin that PEA's are more instructive, while PCP-types turn focus inward. PCP-type compounds are unique among the "hallucinogens" in that they have real abuse/addiction potential.

Rhodium

  • Guest
Full Article
« Reply #8 on: May 28, 2002, 06:05:00 AM »