^abcdGlennon RA, Young R (5 August 2011). "Role of Stereochemistry in Drug Discrimination Studies".Drug Discrimination. Wiley. pp. 129–161.doi:10.1002/9781118023150.ch4.ISBN978-0-470-43352-2. Retrieved22 May 2025.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.
^abcdefghijklmGlennon RA, Young R, Rangisetty JB (May 2002). "Further characterization of the stimulus properties of 5,6,7,8-tetrahydro-1,3-dioxolo[4,5-g]isoquinoline".Pharmacol Biochem Behav.72 (1–2):379–387.doi:10.1016/s0091-3057(01)00768-7.PMID11900809.
^abcdefghMalmusi L, Dukat M, Young R, Teitler M, Darmani NA, Ahmad B, Smith C, Glennon RA (January 1996). "1,2,3,4-Tetrahydroisoquinoline analogs of phenylalkylamine stimulants and hallucinogens".Medicinal Chemistry Research.6 (6):400–411.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.
^abcMalmusi L, Dukat M, Young R, Teitler M, Darmani NA, Ahmad B, Smith C, Glennon RA (June 1996). "1,2,3,4-Tetrahydroisoquinoline and related analogs of the phenylalkylamine designer drug MDMA".Medicinal Chemistry Research.6 (6):412–426.1,2,3,4-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.
^abYoung R, Glennon RA (2002). "The stimulus effect of 5,6,7,8-tetrahydro-1,3-dioxolo[4,5-g]isoquinoline is similar to that of cocaine but different from that of amphetamine".Pharmacol Biochem Behav.71 (1–2):205–213.doi:10.1016/s0091-3057(01)00666-9.PMID11812524.
