Antinociceptive effects of the novel spirocyclopiperazinium salt compound LXM-10 in mice.
The compound LXM-10 (2,4-dimethyl-9-beta-phenylethyl-3-oxo-6, 9-diazaspiro [5.5]undecane chloride) is a new spirocyclopiperazinium salt compound. This is the first article to evaluate its antinociceptive effect in the abdominal constriction test induced by acetic acid and the hot-plate test. In the abdominal constriction test, LXM-10 had a significant dose-response effect, and the maximal inhibition ratio was 79.2%. In the hot-plate test, LXM-10 had significant dose-response and time-response effects. The antinociceptive effect began at 1.0 h, peaked at 2.0 h, and persisted 3.0 h after s.c. administration. The hot-plate latency was increased by 126.8% at the dose of 12.0 mg/kg. The antinociceptive effect of LXM-10 was blocked by mecamylamine (a central and peripheral neuronal nicotinic acetylcholine receptor antagonist, 0.25, 0.5, 1.0 mg/kg, i.p.), hexamethonium (a peripheral neuronal nicotinic acetylcholine receptor antagonist, 0.2, 1.0, 5.0 mg/kg, i.p.), atropine (a central and peripheral muscarinic acetylcholine receptor antagonist, 0.2, 1.0, 5.0 mg/kg, i.p.), and atropine methylnitrate (a peripheral muscarinic acetylcholine receptor antagonist, 0.2, 1.0, 5.0 mg/kg, i.p.) in a dose-dependent fashion. In contrast, the effect was not blocked by naloxone (a non-selective opioid receptor antagonist, 2.0 mg/kg, i.p.) or yohimbine (a alpha(2)-adrenergic receptor antagonist, 1.0, 2.5, 5.0 mg/kg, i.p.) in the hot-plate test. Therefore, the antinociceptive effects of LXM-10 involve the peripheral neuronal nicotinic and muscarinic acetylcholine receptors; they are not related to opioid receptors or alpha(2)-adrenergic receptors. LXM-10 did not affect motor coordination, spontaneous activity, or body temperature. These findings with LXM-10 suggest that spirocyclopiperazinium derivatives could provide insight on new analgesics.
Yue
Cai-Qin
CQ
Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Sciences, Peking University, Beijing, 100083, PR China.
Ye
Jia
J
Li
Chang-Ling
CL
Li
Run-Tao
RT
Sun
Qi
Q
D000700:Analgesics / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001286:Atropine Derivatives / Q000494:pharmacology; D001831:Body Temperature / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D005260:Female; D018738:Hexamethonium / Q000494:pharmacology; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy / Q000503:physiopathology; D010147:Pain Measurement; D010879:Piperazines / Q000737:chemistry / Q000494:pharmacology*; D011597:Psychomotor Performance / Q000187:drug effects; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects / Q000502:physiology; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000502:physiology; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology; D015016:Yohimbine / Q000494:pharmacology
D000700:Analgesics; D001286:Atropine Derivatives; D010879:Piperazines; D018341:Receptors, Adrenergic, alpha-2; D011976:Receptors, Muscarinic; D011978:Receptors, Nicotinic; D011957:Receptors, Opioid; D015016:Yohimbine; D009270:Naloxone; D018738:Hexamethonium; D008464:Mecamylamine; D001285:Atropine; C006649:methylatropine