DOB-CR

DOB-CR
Clinical data
Other names	DOB/CR; "DOB-Conformationally Restrained"; 5,8-Dimethoxy-7-bromo-THIQ; 7-Bromo-5,8-dimethoxy-THIQ; DOB-THIQ; DOB/THIQ
Drug class	Serotonin receptor modulator
ATC code	None;
Identifiers
	IUPAC name 7-bromo-5,8-dimethoxy-1,2,3,4-tetrahydroisoquinoline;
CAS Number	183429-24-5;
PubChem CID	9838353;
ChemSpider	8014073;
Chemical and physical data
Formula	C11H14BrNO2
Molar mass	272.142 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES COC1=CC(=C(C2=C1CCNC2)OC)Br;
	InChI 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.^[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-HT_2A receptor.^[1]^[3] Its affinity (K_i) 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]

References

^ ^a ^b ^c ^d ^e ^f ^g ^h 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)
^ ^a ^b ^c ^d ^e 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.
^ ^a ^b ^c ^d ^e ^f ^g ^h 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.
^ ^a ^b ^c ^d ^e ^f 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.