Chemistry:DOB-CR

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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.[1][2][3][4] 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.[1][2][4][3]

Pharmacology

The drug shows modest affinity for the serotonin 5-HT2A receptor.[1][3] Its affinity (Ki) for the receptor was 242 to 250 nM, which is about 6-fold lower than that of DOB.[1][3] In contrast to DOB, DOB-CR completely failed to substitute for DOM in rodent drug discrimination tests.[1][2][3][4] In addition, behavioral disruption occurred at higher doses.[1][3] These findings suggest that DOB-CR would lack psychedelic effects in humans.[1][2][3][4] The drug also failed to substitute for dextroamphetamine and MDMA in rodent drug discrimination tests, suggesting lack of stimulant or entactogenic effects as well.[4] 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.[2][4]

History

DOB-CR was first described in the scientific literature by Richard Glennon and colleagues by 1996.[1][3]

See also

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 (in de) Phenethylamine: von der Struktur zur Funktion. Nachtschatten-Science (1 ed.). Solothurn: Nachtschatten-Verlag. 2013. pp. 866. ISBN 978-3-03788-700-4. OCLC 858805226. https://books.google.com/books?id=-Us1kgEACAAJ. 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. ↑ 2.0 2.1 2.2 2.3 2.4 "Role of Stereochemistry in Drug Discrimination Studies". Drug Discrimination. Wiley. 5 August 2011. pp. 129–161. doi:10.1002/9781118023150.ch4. ISBN 978-0-470-43352-2. https://onlinelibrary.wiley.com/doi/10.1002/9781118023150.ch4. 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. ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 "1,2,3,4-Tetrahydroisoquinoline analogs of phenylalkylamine stimulants and hallucinogens.". Medicinal Chemistry Research 6 (6): 400–411. January 1996. "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. ↑ 4.0 4.1 4.2 4.3 4.4 4.5 "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. May 2002. doi:10.1016/s0091-3057(01)00768-7. PMID 11900809. 




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