A-69024
 | |
| Clinical data | |
|---|---|
| Other names | A69024; 1-(2-Bromo-4,5-dimethoxybenzyl)-7-hydroxy-6-methoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline |
| Routes of administration | Unknown[1] |
| Drug class | Dopamine D1 receptor antagonist |
| Identifiers | |
| |
| CAS Number | |
| PubChem CID | |
| ChemSpider | |
| CompTox Dashboard (EPA) | |
| Chemical and physical data | |
| Formula | C20H24BrNO4 |
| Molar mass | 422.319 g·mol−1 |
| 3D model (JSmol) | |
| |
| |
A-69024 is a selective dopamine D1 receptor antagonist which was under development for the treatment of psychotic disorders but was never marketed.[1][2][3] Its route of administration is unknown.[1]
Pharmacology
[edit]Pharmacodynamics
[edit]A-69024 is a selective dopamine D1 receptor antagonist.[3] It shows high affinity for this receptor (Ki = 5.3–12.6 nM) and high selectivity for it over the dopamine D2 receptor (Ki = 1,290–1,320 nM; 102- to 249-fold lower affinity).[3] Conversely, the drug shows very low affinity for the serotonin 5-HT2A and 5-HT2C receptors (Ki = >10,000 nM).[4][3] On the other hand, it shows some affinity for the α2-adrenergic receptor (Ki = 95.5 nM) but not for the α1-adrenergic receptor (Ki = >1,000 nM).[4]
A-69024 blocks amphetamine- and cocaine-induced hyperlocomotion and apomorphine-induced stereotypy in rodents.[3][5] It does not affect prolactin levels in rodents, unlike dopamine D2 receptor modulators.[3] Along with SCH-23390, it produces aversive effects in rodents, whereas dopamine D2 receptor antagonists like spiperone and levosulpiride do not do so.[6] The drug increases cocaine self-administration in rodents.[7] Along with other dopamine D1 receptor antagonists, A-69024 has been found to block the head-twitch response induced by the serotonergic psychedelic DOI.[4] Similarly, dopamine D2 receptor antagonists were likewise found to block the DOI-induced head-twitch response.[4]
Pharmacokinetics
[edit]A-69024 showed poor oral bioavailability of less than 2.5% in rodents.[3] As such, it is instead administered parenterally.[3]
Chemistry
[edit]Analogues
[edit]Radiolabeled forms of A-69024 have been developed and studied, for instance for potential use in positron emission tomography (PET) imaging.[8][9][10][11][12][13]
History
[edit]A-69024 was first described in the scientific literature by 1989.[3] It was under development by Abbott Laboratories.[1][2] The drug reached the preclinical research stage of development prior to the discontinuation of its development in 1994.[1][2]
See also
[edit]References
[edit]- 1 2 3 4 5 "A 69024". AdisInsight. 5 February 2013. Retrieved 7 June 2026.
- 1 2 3 "Delving into the Latest Updates on A-69024 with Synapse". Synapse. 28 March 2026. Retrieved 7 June 2026.
- 1 2 3 4 5 6 7 8 9 Kerkman DJ, Ackerman M, Artman LD, MacKenzie RG, Johnson MC, Bednarz L, et al. (August 1989). "A-69024: a non-benzazepine antagonist with selectivity for the dopamine D-1 receptor". European Journal of Pharmacology. 166 (3): 481–491. doi:10.1016/0014-2999(89)90362-2. PMID 2509217.
- 1 2 3 4 Schreiber R, Brocco M, Audinot V, Gobert A, Veiga S, Millan MJ (April 1995). "(1-(2,5-dimethoxy-4 iodophenyl)-2-aminopropane)-induced head-twitches in the rat are mediated by 5-hydroxytryptamine (5-HT) 2A receptors: modulation by novel 5-HT2A/2C antagonists, D1 antagonists and 5-HT1A agonists". The Journal of Pharmacology and Experimental Therapeutics. 273 (1): 101–112. doi:10.1016/S0022-3565(25)09485-6. PMID 7714755.
- ↑ Katz JL, Kopajtic TA, Myers KA, Mitkus RJ, Chider M (October 1999). "Behavioral effects of cocaine: interactions with D1 dopaminergic antagonists and agonists in mice and squirrel monkeys". The Journal of Pharmacology and Experimental Therapeutics. 291 (1): 265–279. doi:10.1016/S0022-3565(24)35097-9. PMID 10490913.
- ↑ Shippenberg TS, Bals-Kubik R, Huber A, Herz A (1991). "Neuroanatomical substrates mediating the aversive effects of D-1 dopamine receptor antagonists". Psychopharmacology. 103 (2). Berl: 209–214. doi:10.1007/BF02244205. PMID 1827526.
- ↑ Britton DR, Curzon P, Mackenzie RG, Kebabian JW, Williams JE, Kerkman D (August 1991). "Evidence for involvement of both D1 and D2 receptors in maintaining cocaine self-administration". Pharmacology, Biochemistry, and Behavior. 39 (4): 911–915. doi:10.1016/0091-3057(91)90052-4. PMID 1684870.
- ↑ Kassiou M, Scheffel UA, Musachio JL, Stathis M, Dannals RF (1995). "[3H]A-69024: a non-benzazepine ligand for in vitro and in vivo studies of dopamine D1 receptors". Life Sciences. 57 (23): PL367–PL372. doi:10.1016/0024-3205(95)02212-2. PMID 7475960.
- ↑ Kassiou M, Scheffel U, Ravert HT, Mathews WB, Musachio JL, Lambrecht RM, et al. (February 1995). "[11C]A-69024: a potent and selective non-benzazepine radiotracer for in vivo studies of dopamine D1 receptors". Nuclear Medicine and Biology. 22 (2): 221–226. doi:10.1016/0969-8051(94)00086-y. PMID 7767316.
- ↑ Kassiou M, Mardon K, Mattner F, Katsifis A, Dikic B (June 2001). "Pharmacological evaluation of (+)-2- [123I]A-69024: a radioligand for in vivo studies of dopamine D1 receptors". Life Sciences. 69 (6): 669–675. doi:10.1016/s0024-3205(01)01156-0. PMID 11476188.
- ↑ Rice OV, Gatley SJ, Shen J, Huemmer CL, Rogoz R, DeJesus OT, et al. (November 2001). "Effects of endogenous neurotransmitters on the in vivo binding of dopamine and 5-HT radiotracers in mice". Neuropsychopharmacology. 25 (5): 679–689. doi:10.1016/S0893-133X(01)00287-1. PMID 11682251.
- ↑ Kassiou M, Loc'h C, Bottlaender M, Mardon K, Ottaviani M, Coulon C, et al. (April 2002). "(+)-[76Br]A-69024: a non-benzazepine radioligand for studies of dopamine D1 receptors using PET". Nuclear Medicine and Biology. 29 (3): 295–302. doi:10.1016/s0969-8051(01)00306-7. PMID 11929698.
- ↑ Besret L, Dollé F, Hérard AS, Guillermier M, Demphel S, Hinnen F, et al. (July 2008). "Dopamine D1 receptor imaging in the rodent and primate brain using the isoquinoline +-[11C]A-69024 and positron emission tomography". Journal of Pharmaceutical Sciences. 97 (7): 2811–2819. Bibcode:2008JPhmS..97.2811B. doi:10.1002/jps.21168. PMID 17786986.
