Chemistry:A-69024
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
Pharmacodynamics
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
A-69024 showed poor oral bioavailability of less than 2.5% in rodents.[3] As such, it is instead administered parenterally.[3]
Chemistry
Analogues
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
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
References
- ↑ 1.0 1.1 1.2 1.3 "A 69024". 5 February 2013. https://adisinsight.springer.com/drugs/800002637.
- ↑ 2.0 2.1 2.2 "Delving into the Latest Updates on A-69024 with Synapse". 28 March 2026. https://synapse.patsnap.com/drug/2bcf1aa83ef74ca6b21118b241268498.
- ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 3.8 "A-69024: a non-benzazepine antagonist with selectivity for the dopamine D-1 receptor". European Journal of Pharmacology 166 (3): 481–491. August 1989. doi:10.1016/0014-2999(89)90362-2. PMID 2509217.
- ↑ 4.0 4.1 4.2 4.3 "(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. April 1995. doi:10.1016/S0022-3565(25)09485-6. PMID 7714755.
- ↑ "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. October 1999. doi:10.1016/S0022-3565(24)35097-9. PMID 10490913.
- ↑ "Neuroanatomical substrates mediating the aversive effects of D-1 dopamine receptor antagonists". Psychopharmacology (Berl) 103 (2): 209–214. 1991. doi:10.1007/BF02244205. PMID 1827526.
- ↑ "Evidence for involvement of both D1 and D2 receptors in maintaining cocaine self-administration". Pharmacology, Biochemistry, and Behavior 39 (4): 911–915. August 1991. doi:10.1016/0091-3057(91)90052-4. PMID 1684870.
- ↑ "[3H]A-69024: a non-benzazepine ligand for in vitro and in vivo studies of dopamine D1 receptors". Life Sciences 57 (23): PL367–PL372. 1995. doi:10.1016/0024-3205(95)02212-2. PMID 7475960.
- ↑ "[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. February 1995. doi:10.1016/0969-8051(94)00086-y. PMID 7767316.
- ↑ "Pharmacological evaluation of (+)-2- [123I]A-69024: a radioligand for in vivo studies of dopamine D1 receptors". Life Sciences 69 (6): 669–675. June 2001. doi:10.1016/s0024-3205(01)01156-0. PMID 11476188.
- ↑ "Effects of endogenous neurotransmitters on the in vivo binding of dopamine and 5-HT radiotracers in mice". Neuropsychopharmacology 25 (5): 679–689. November 2001. doi:10.1016/S0893-133X(01)00287-1. PMID 11682251.
- ↑ "(+)-[76Br]A-69024: a non-benzazepine radioligand for studies of dopamine D1 receptors using PET". Nuclear Medicine and Biology 29 (3): 295–302. April 2002. doi:10.1016/s0969-8051(01)00306-7. PMID 11929698.
- ↑ "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. July 2008. doi:10.1002/jps.21168. PMID 17786986. Bibcode: 2008JPhmS..97.2811B.
 |  |
