Effects of rat/mouse hemokinin-1, a mammalian tachykinin peptide, on the antinociceptive activity of pethidine administered at the peripheral and supraspinal level.
We have recently reported that rat/mouse hemokinin-1 (r/m HK-1), a mammalian tachykinin, produced dose- and time-related antinociceptive effects at the supraspinal level via activating NK(1) receptors. Moreover, r/m HK-1 remarkably enhanced both the antinociceptive extent and duration of morphine administered at the peripheral and supraspinal level through a convergence of pharmacological effects of opioid-responsive neurons. Pethidine hydrochloride is an important narcotic analgesic, which acts as an opiate agonist and has pharmacological effects similar to morphine. To improve our knowledge of the pharmacology of pethidine, the aim of the present study was to investigate the relationship between the nociception of r/m HK and pethidine by comparing it with that of r/m HK-1 and morphine. Our data showed that r/m HK-1 remarkably enhanced the antinociceptive extent of pethidine administered at the peripheral level, but not at the supraspinal level. These antinociceptive effects were blocked by prior treatment with the classical opioid receptor antagonist naloxone, indicating that the potentiated analgesic effect is mediated by opioid-responsive neurons. Differences in the antinociceptive activity of pethidine and morphine in combination with r/m HK-1, arise because there are differences in the physicochemical and pharmacokinetic properties of pethidine and morphine, particularly their lipophilicity. Our results may pave the way for a new strategy for the control of pain and may provide a clinical strategy to enable selection of either opioid as a priority.
Fu
Cai-Yun
CY
Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Institute of Biochemistry and Molecular Biology, Lanzhou University, 222 Tian Shui South Road, Lanzhou 730000, People's Republic of China.
Tang
Xiao-Long
XL
Yang
Qi
Q
Chen
Qiang
Q
Wang
Rui
R
D000701:Analgesics, Opioid / Q000008:administration & dosage*; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D004347:Drug Interactions; D007276:Injections, Intraventricular / Q000379:methods; D008297:Male; D008614:Meperidine / Q000008:administration & dosage*; D051379:Mice; D008815:Mice, Inbred Strains; D010146:Pain / Q000188:drug therapy*; D010147:Pain Measurement / Q000379:methods; D011930:Reaction Time / Q000187:drug effects; D015320:Tachykinins / Q000008:administration & dosage*; D013997:Time Factors
D000701:Analgesics, Opioid; D015320:Tachykinins; C507968:hemokinin-1; D008614:Meperidine