DOB-CR

DOB-CR
Clinical data
Other namesDOB/CR; "DOB-Conformationally Restrained"; 5,8-Dimethoxy-7-bromo-THIQ; 7-Bromo-5,8-dimethoxy-THIQ; DOB-THIQ; DOB/THIQ
Drug classSerotonin receptor modulator
ATC code
  • None
Identifiers
  • 7-bromo-5,8-dimethoxy-1,2,3,4-tetrahydroisoquinoline
CAS Number
PubChem CID
ChemSpider
Chemical and physical data
FormulaC11H14BrNO2
Molar mass272.142 g·mol−1
3D model (JSmol)
  • COC1=CC(=C(C2=C1CCNC2)OC)Br
  • InChI=1S/C11H14BrNO2/c1-14-10-5-9(12)11(15-2)8-6-13-4-3-7(8)10/h5,13H,3-4,6H2,1-2H3
  • Key:YDHKNGFINXQAKM-UHFFFAOYSA-N

DOB-CR, or DOB/CR, an acronym of "DOB-conformationally restrained", also known as 7-bromo-5,8-dimethoxy-1,2,3,4-tetrahydroisoquinoline, is a serotonin receptor modulator of the tetrahydroisoquinoline family. It is a cyclized phenethylamine and a derivative of the psychedelic drugs 2C-B and DOB in which the side chain has been cyclized with the benzene ring to form a tetrahydroisoquinoline (THIQ) ring system.

Pharmacology

The drug shows modest affinity for the serotonin 5-HT2A receptor. Its affinity (Ki) for the receptor was 242 to 250 nM, which is about 6-fold lower than that of DOB. In contrast to DOB, DOB-CR completely failed to substitute for DOM in rodent drug discrimination tests. In addition, behavioral disruption occurred at higher doses. These findings suggest that DOB-CR would lack psychedelic effects in humans. The drug also failed to substitute for dextroamphetamine and MDMA in rodent drug discrimination tests, suggesting lack of stimulant or entactogenic effects as well. However, DOB-CR fully substituted for the structurally related selective α2-adrenergic receptor ligand TDIQ (MDTHIQ or MDA-CR), albeit with about 4-fold lower potency than TDIQ itself.

History

DOB-CR was first described in the scientific literature by Richard Glennon and colleagues by 1996.

See also

References

  1. 1 2 3 4 5 6 7 8 Trachsel D, Lehmann D, Enzensperger C (2013). Phenethylamine: von der Struktur zur Funktion [Phenethylamines: From Structure to Function]. Nachtschatten-Science (in German) (1 ed.). Solothurn: Nachtschatten-Verlag. p. 866. ISBN 978-3-03788-700-4. OCLC 858805226. Retrieved 31 January 2025. Die Tetrahydroisochinolin-THIQ)-Analoga 437 und 438 wurden als rigide Analoga von DOM (8) und DOB (2) untersucht. Sie waren jeweils deutlich weniger affin zum 5-HT Rezeptor als ihre Analoga [1821. Weiter vermochten sie in einer Diskriminationsstudie keinen Stimulus in DOM-trainierten Ratten zu erzeugen. [...] 437 Ki, h5-HT2A: 2150nM ([3H]Ketanserin) (Ki DOM: 100nM) [...] 438 Ki h5-HT2A: 242nM ([3H]Ketanserin) (Ki DOB: 41 nM)
  2. 1 2 3 4 5 Glennon RA, Young R (5 August 2011). "Role of Stereochemistry in Drug Discrimination Studies". Drug Discrimination. Wiley. pp. 129–161. doi:10.1002/9781118023150.ch4. ISBN 978-0-470-43352-2. Retrieved 22 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.
  3. 1 2 3 4 5 6 7 8 Malmusi L, Dukat M, Young R, Teitler M, Darmani NA, Ahmad B, et al. (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.
  4. 1 2 3 4 5 6 Glennon 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". Pharmacology, Biochemistry, and Behavior. 72 (1–2): 379–387. doi:10.1016/s0091-3057(01)00768-7. PMID 11900809.