The interaction between gamma-aminobutyric acid agonists and diltiazem in visceral antinociception in rats.
To examine whether the gamma-aminobutyric acid (GABA) receptor agonists and L-type voltage-dependent calcium channel blockers potentiate each other on the visceral antinociceptive effects at the spinal cord, we assessed visceral nociception with colorectal distension (CD) test in rats with an intrathecal catheter. The measurements were performed after intrathecal administration of a GABA agonist (muscimol or baclofen), a calcium channel blocker (diltiazem), or the combination of the two. CD threshold did not change after muscimol 0.1 microg, baclofen 0.01 microg, or diltiazem 100 microg, but increased slightly after muscimol 1 microg and baclofen 0.1 microg. When muscimol 0.1 microg or 1 microg was administered with diltiazem, the increase in CD threshold was significantly larger than muscimol alone (at 5 min, 26.2% versus 0.6% MPE (maximum possible effect) or 84.5% versus 19.5%MPE, respectively; P < 0.01). The CD threshold after the combination of baclofen 0.1 microg and diltiazem also showed a significantly larger increase than that seen after baclofen alone (at 5 min, 48.0% versus 14.3% MPE; P < 0.01). Motor paralysis observed with muscimol 1 microg did not increase when muscimol was coadministered with diltiazem. In conclusion, intrathecal diltiazem in combination with a GABA agonist, muscimol or baclofen, potentiated the GABA agonists-induced visceral antinociception without increasing motor paralysis.


CONCLUSIONS
Intrathecal administration of diltiazem in combination with a gamma-aminobutyric acid (GABA) agonist, muscimol or baclofen, potentiated the GABA agonists-induced visceral antinociception but did not affect motor paralysis. The present results indicate that the coadministration of the two types of drugs may be clinically useful.
Hara
Kaoru
K
Department of Anesthesiology, Shimane University School of Medicine, Izumo City, Japan. ccy79350@hkg.odn.ne.jp
Saito
Yoji
Y
Kirihara
Yumiko
Y
Sakura
Shinichi
S
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000187:drug effects; D002404:Catheterization; D003106:Colon / Q000502:physiology; D004110:Diltiazem / Q000494:pharmacology*; D004357:Drug Synergism; D018755:GABA Agonists / Q000494:pharmacology*; D058785:GABA-A Receptor Agonists; D058786:GABA-B Receptor Agonists; D007278:Injections, Spinal; D008297:Male; D009068:Movement / Q000187:drug effects; D009118:Muscimol / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy*; D010147:Pain Measurement / Q000187:drug effects; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012007:Rectum / Q000502:physiology; D013116:Spinal Cord / Q000187:drug effects
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D018755:GABA Agonists; D058785:GABA-A Receptor Agonists; D058786:GABA-B Receptor Agonists; D009118:Muscimol; D004110:Diltiazem