Antinociceptive mechanisms of dipsacus saponin C administered intracerebroventricularly in the mouse.
1. Dipsacus saponin C (DSC) administered intracerebroventricularly (i.c.v.) showed an antinociceptive effect in a dose-dependent (from 3.75 to 30 micrograms) manner as measured by the tailflick assay. The antinociception induced by DSC at the dose of 30 micrograms was maintained at least 1 h. 2. Sulfated cholecystokinin (CCK, from 0.1 to 0.5 ng); muscimol (a GABAA receptor agonist, from 50 to 200 ng); MK-801 [(+/-)-5-methyl-10, 11-dihydro-5H-dibenzo (a,d) cyclohepten-5, 10-imine maleate, from 0.1 to 1 microgram], a noncompetitive N-methyl-D-aspartic acid (NMDA) receptor antagonist; or CNQX (6-cyano-7-nitroquinoxaline-2,3-dione, from 0.1 to 0.5 microgram), a non-NMDA receptor antagonist, injected i.c.v. significantly reduced the inhibition of the tail-flick response induced by DSC (30 micrograms) administered i.c.v. However, naloxone (an opioid receptor antagonist, 2 micrograms) or baclofen (a GABAB receptor antagonist, 10 ng) did not affect the inhibition of the tail-flick response induced by DSC. 3. The intrathecal (i.t.) injection of yohimbine (an alpha 2-adrenergic receptor antagonist, from 5 to 20 micrograms) and methysergide (a serotonin receptor antagonist, from 5 to 20 micrograms) but not naloxone (from 2 to 8 micrograms), significantly attenuated inhibition of the tail-flick response induced by DSC (30 micrograms) administered i.c.v. 4. Our results suggest that DSC has an antinociceptive effect when it is administered supraspinally and GABAA, NMDA and non-NMDA receptors, but not opioid and GABAB receptors located at the supraspinal level, may be involved in DSC-induced antinociception. Furthermore, DSC administered supraspinally may produce antinociception by stimulating descending alpha 2-adrenergic and serotonin pathways but not the opioidergic pathway.
Suh
H W
HW
Institute of Natural Medicine, College of Medicine, Hallym University, Kangwon-Do, South Korea.
Song
D K
DK
Son
K H
KH
Wie
M B
MB
Lee
K H
KH
Jung
K Y
KY
Do
J C
JC
Kim
Y H
YH
D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D002240:Carbohydrate Sequence; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000494:pharmacology*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008969:Molecular Sequence Data; D009828:Oleanolic Acid / Q000031:analogs & derivatives*; D010147:Pain Measurement / Q000187:drug effects; D011930:Reaction Time / Q000187:drug effects; D011949:Receptors, Cholecystokinin / Q000187:drug effects / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000037:antagonists & inhibitors; D012503:Saponins / Q000008:administration & dosage / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D000700:Analgesics; D004365:Drugs, Chinese Herbal; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018755:GABA Agonists; D018756:GABA Antagonists; D011949:Receptors, Cholecystokinin; D016194:Receptors, N-Methyl-D-Aspartate; D012503:Saponins; D017366:Serotonin Receptor Agonists; C085394:dipsacus saponin C; D009828:Oleanolic Acid