N-oleoyl-dopamine decreases muscle rigidity induced by reserpine in rats.
N-oleoyl-dopamine (OLDA), a product of condensation of oleic acid and dopamine (DA), is a bioactive compound that crosses the blood-brain barrier after systemic administration. The possibility arises that OLDA could have a potential role in treating DA-related disorders, such as Parkinsons disease (PD). In the present study we seek to determine whether OLDA would affect muscle tone and akinesia in two rat models of PD: the reserpine-evoked muscle rigidity and the reserpine- and haloperidol-induced catalepsy. We found that OLDA (20 mg/kg) significantly decreased muscle rigidity induced by reserpine (2.5 mg/kg), measured as an increased mechanical muscle resistance (MMG) in response to a passive extension and flexion of a rat hind limb at the ankle joint. Moreover, OLDA potently decreased the reserpine-enhanced tonic and reflex electromyographic (EMG) activities recorded before and during the movement, respectively. A lower dose of OLDA (10 mg/kg) failed to have appreciable effects. The reference compound L-DOPA (25 mg/kg) also attenuated the reserpine-increased MMG and EMG activities; the effects were, however, observed much later and were less prominent than those characteristic of OLDA. In contrast to the effects on muscle tone, OLDA (20 and 40 mg/kg) did not influence catalepsy induced by either reserpine (1.25 mg/kg) or haloperidol (0.5 mg/kg). In conclusion, the study demonstrates a novel biological action of N-oleoyl-dopamine consisting of lowering the reserpine-induced muscle rigidity. However, the lack of influence on akinesia suggests that the compound has myorelaxant rather than anti-Parkinsonian properties.
Konieczny
J
J
Department of Neuropsychopharmacology, Institute of Pharmacology, Polish Academy of Sciences, Cracow, Poland.
Przegalinski
E
E
Pokorski
M
M
D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology; D004298:Dopamine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D004576:Electromyography / Q000187:drug effects; D006220:Haloperidol / Q000494:pharmacology; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D009127:Muscle Rigidity / Q000139:chemically induced / Q000188:drug therapy*; D051381:Rats; D017208:Rats, Wistar; D012110:Reserpine / Q000494:pharmacology
D000978:Antiparkinson Agents; D007980:Levodopa; D012110:Reserpine; D006220:Haloperidol; C488796:N-oleoyldopamine; D004298:Dopamine