Oleic Derivatives of Dopamine and Respiration.
Adv Exp Med Biol
; 1023: 37-46, 2018.
Article
em En
| MEDLINE
| ID: mdl-28681186
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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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Respiração
/
Dopamina
/
Ácido Oleico
Limite:
Animals
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article