The cerebrovascular and anti-ischemic effects of dopamine and synthetic docosahexaenoyldopamine (DHA-DA) and the GABA–DHA-DA conjugate (OXL1220) were compared and found to differ. Dopamine and DHA-DA increased blood flow in intact and ischemic brain that was associated with pronounced hypertensive reactions. The latter inhibited dopamine transporter with IC50 = 29 μM but was practically inactive as a ligand for dopamine receptors. OXL1220 produced a selective vasodilating effect on blood flow in brain subjected to transient global ischemia. Only OXL1220 competed in vitro for specific binding sites of [3H]-gabazine in rat-brain GABAA-receptors. Therefore, conjugation of a neuromediator (GABA) to the DHA-DA changed the dopaminergic activity of the compound to GABA-ergic with respect to vascular tone in ischemic brain.
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Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 49, No. 10, pp. 19 – 24, October, 2015.
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Mirzoyan, R.S., Gan’shina, T.S., Topchyan, A.V. et al. Differences Between Cerebrovascular and Anti-Ischemic Effects of Dopamine, Docosahexaenoyldopamine, and GABA–Docosahexaenoyldopamine Conjugate. Pharm Chem J 49, 661–666 (2016). https://doi.org/10.1007/s11094-016-1348-7
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DOI: https://doi.org/10.1007/s11094-016-1348-7