Abstract
Lipid derivatives of dopamine are a new class of substances with dopamine-like activity and of potential use in the field of neurodegenerative disorders. However, the interaction of such compounds with the respiratory system remains unclear. The aim of the study was to examine how three main members of this class, N-oleoyl-dopamine (OLDA), 3'-O-methyl-N-oleoyl-dopamine (OMeOLDA) and 3'-O-oleoyl-N-oleoyl-dopamine (OLOLDA) would influence the hypoxic ventilator response (HVR) of the rat. The study was performed in 20 rats conscious rats. Ventilation and its responses to 8% O2 in N2 were measured in a whole body plethysmographic chamber. The findings were that OLDA decreased the peak hypoxic ventilatory response from 2279.0 ±237.8 to 1338.3 ±49.5 ml·min-1·kg-1, OMeOLDA - from 1698.3 ±88.2 to 1433.8± 97.4 ml·min-1·kg-1, and OLOLDA – from 1885.9 ±52.2 to 1530.4 ±56.3 ml·min-1·kg-1; the decreases amounted to 46, 16, and 25%, respectively (p<0.05 each). These results show that the lipid-derivatives of dopamine are inhibitory for ventilation, acting like exogenously applied dopamine. We conclude that blockade of the 3' hydroxyl group of the dopamine ring, particularly with the methyl group, decreases dopamine-like inhibitory activity toward ventilation. Thus, the potential use of OMeOLDA as a carrier of dopamine into the brain seems the best choice as the compound is least inhibitory for ventilation which may already be decreased in neurodegenerative conditions.
- © 2014 ERS