Abstract
Ventilatory inhibition is considered an undesirable pharmacological side effect of pharmacotherapy in neurodegenerative conditions underlain by brain dopamine deficiency. In this context, oleic derivatives of dopamine or N-acyl-dopamines are novel substances that may be of high therapeutic interest as having the ability to cross the blood-brain barrier and acting in dopamine-like manner. In the present study we seek to define the influence of N-acyl-dopamines on lung ventilation and its hypoxic responses in the rat. We found that N-oleoyl-dopamine decreased both normoxic and peak hypoxic ventilation in response to 8% acute hypoxia, on average, by 31% and 41%, respectively. Its metabolite, 3′-O-methyl-N-oleoyl-dopamine, caused a 15% ventilatory decrease each, whereas an oleic ester derivative, 3′-O-oleoyl-N-oleoyl-dopamine, caused 11% and 19% ventilatory decreases, respectively. All three N-acyl-dopamines investigated displayed an inhibitory effect on ventilation. The findings indicate that 3′-O-methyl-N-oleoyl-dopamine and 3′-O-oleoyl-N-oleoyl-dopamine performed better than N-oleoyl-dopamine in term of less ventilatory suppression, albeit the differences among the three compounds were modest. We conclude that N-acyl-dopamines are worthy of intensified explorations as potential carriers of dopamine molecule in view of the lack of clinically effective methods of dopamine delivery into the brain in neurodegenerative conditions.
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Conflicts of Interest
The authors of this work are inventors of the European and US patents covering the medical applications of OMe-OLDA supported in part by the EU Innovative Economy grant POIG 1.3.2.-14–047/11.
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Zajac, D., Stasinska, A., Pokorski, M. (2017). Oleic Derivatives of Dopamine and Respiration. In: Pokorski, M. (eds) Pulmonary Disorders and Therapy. Advances in Experimental Medicine and Biology(), vol 1023. Springer, Cham. https://doi.org/10.1007/5584_2017_73
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DOI: https://doi.org/10.1007/5584_2017_73
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