Effects of diltiazem and MK-801 on morphine analgesia and pharmacokinetics in mice.
The effects of diltiazem, an L-type calcium channel blocker, and MK-801, a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist on morphine analgesia and pharmacokinetics were examined in mice. Mice received a subcutaneous injection of morphine (3.2 mg/kg) 30 min after a subcutaneous injection of diltiazem or MK-801. Diltiazem (20-60 mg/kg) potentiated morphine analgesia and increased serum morphine levels in a dose-dependent manner. MK-801 (0.3 mg/kg) significantly attenuated morphine analgesia but had no significant effect on serum or brain morphine levels. These results suggest that a modification of morphine metabolism is involved, at least in part, in the ability of diltiazem to enhance morphine analgesia, whereas MK-801 attenuates morphine analgesia without affecting morphine pharmacokinetics.
Maeda
Takehiko
T
Department of Pharmacology, Wakayama Medical University, 811-1 Kimiidera, Wakayama-City, Wakayama 641-0012, Japan.
Kishioka
Shiroh
S
Fan
Xintian
X
Fukazawa
Yohji
Y
Shimizu
Norifumi
N
Ozaki
Masanobu
M
Yamamoto
Hiroyuki
H
D000698:Analgesia; D000818:Animals; D001921:Brain / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004110:Diltiazem / Q000494:pharmacology*; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors
D002121:Calcium Channel Blockers; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D009020:Morphine; D004110:Diltiazem