DOM-CR, or DOM/CR, an acronym of "DOM-conformationally restrained", is a tetrahydroisoquinoline (THIQ) and cyclized phenethylamine related to the psychedelics DOM and 2C-D.[1][2][3] It is a cyclized THIQ analogue of DOM and 2C-D.[1][2][3]
In contrast to DOM, DOM-CR does not substitute for DOM in rodent drug discrimination tests, suggesting that it lacks psychedelic effects.[1][2][3] Similarly, DOM-CR does not substitute for dextroamphetamine or MDMA, suggesting that it likewise lacks stimulant or entactogenic effects.[2] However, DOM-CR does substitute for TDIQ (MDTHIQ), a selective α2-adrenergic receptor ligand.[1][2] At high doses, DOM-CR produces behavioral disruption in drug discrimination tests.[2] In contrast to DOM and amphetamine, DOM-CR does not produce hyperlocomotion in rodents.[3] Also unlike DOM, it shows no affinity for the serotonin 5-HT2A receptor.[3]
DOM-CR was first described in the scientific literature by Richard Glennon and colleagues by 1996.[2][3]
Other cyclized THIQ analogues of psychoactive phenethylamines have also been developed and characterized.[2][3][4][5][6] These include AMPH-CR (THIQ), METH-CR (N-methyl-THIQ), TDIQ (MDTHIQ, MDA-CR), TDMIQ (MDMTHIQ, MDMA-CR), N-methyl-DOM-CR (Beatrice-CR), DOB-CR, and PMMA-CR.[2][3][4][5][6] Conformational restriction of stimulant, hallucinogen, and/or entactogen phenethylamines into THIQ analogues, like the preceding compounds, usually abolishes their associated effects as well as their affinities for monoamine transporters and/or serotonin 5-HT2 receptors.[2][4] However, it does not necessarily remove all pharmacological activity, as evidenced by some THIQs interacting with α2-adrenergic receptors[2] as well as serotonin 5-HT1D, 5-HT6, and/or 5-HT7 receptors[2][7][8] and producing behavioral effects in animals.[2]
Other cyclized analogues of DOM and related psychedelics include DOM-AT, DOM-AI, DMCPA, TFMBOX, jimscaline, TCB-2, LPH, and ZC-B.[9][10][11]
Figure 4-13. Chemical structures of TDIQ, and conformationally constrained forms of amphetamine (AMPH-CR), methamphetamine (METH-CR), and the hallucinogens DOM (DOM-CR) and DOB (DOB-CR). [...] Conformationally constrained analogs of the hallucinogens DOM and DOB (i.e., DOM-CR and DOB-CR) were not recognized by rats trained to discriminate 1.0 mg/kg of DOM from saline vehicle, but substituted in rats trained to discriminate TDIQ from vehicle (ED50 = 4.2 and 3.4 mg/kg, respectively) [15]. Interestingly, the TDIQ stimulus did not generalize to the N-methyl analog of DOM-CR [15]. Taken together with the findings obtained for METH-CR, it would appear that N-methylation is not tolerated with regard to producing TDIQ-like discriminative stimulus effects [15]. But, more importantly, and to reiterate what was stated above, it should not be assumed that "inactive" conformationally constrained rotamers are necessarily pharmacologically inactive; results depend on the similarity in the stimulus properties of the training drug and test agent.
Conformationally constrained, 1,2,3,4-tetrahydroisoquinoline (TIQ) analogs of central stimulant (e.g. amphetamine) and hallucinogenic (e.g. DOM) phenylalkylamines were prepared and evaluated to determine the contribution to activity of this conformational restriction. The amphetamine-related TIQs failed to produce locomotor stimulation in mice and did not produce amphetamine-appropriate responding in tests of stimulus generalization in (+)amphetamine-trained rats. Hallucinogen-related TIQs lacked appreciable affinity for 5-HT2A serotonin receptors and did not produce DOM-like effects in tests of stimulus generalization in DOM-trained rats. It is concluded that the phenylalkylamine conformation represented by the TIQs is not a major contributor to these actions.
1,2,3,4-Tetrahydroisoquinoline (TIQ) analogs of 1-(3,4-methylenedioxyphenyl)-2-aminopropane (MDA) and its N-methyl derivative, MDMA, similar in structure to a TIQ metabolite of MDA, were prepared and examined (a) in tests of central stimulant activity in mice, (b) for their ability to bind at human 5-HT2A receptors, and (c) in tests of stimulus generalization in rats trained to discriminate MDMA from vehicle. In general, the TIQ analogs failed to display appreciable activity in any assay system. Conversely, certain 2-aminotetralin and 2-aminoindan analogs were active in the stimulus generalization studies. It is concluded that TIQ-like conformations do not account for the actions typically associated with MDA- and MDMA-related agents.