title: Effects of diltiazem and MK-801 on morphine analgesia and pharmacokinetics in mice.
abstract: 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.
authors.affiliation: Department of Pharmacology, Wakayama Medical University, 811-1 Kimiidera, Wakayama-City, Wakayama 641-0012, Japan.
authors.forename: Takehiko
authors.initials: T
authors.lastname: Maeda
authors.forename: Shiroh
authors.initials: S
authors.lastname: Kishioka
authors.forename: Xintian
authors.initials: X
authors.lastname: Fan
authors.forename: Yohji
authors.initials: Y
authors.lastname: Fukazawa
authors.forename: Norifumi
authors.initials: N
authors.lastname: Shimizu
authors.forename: Masanobu
authors.initials: M
authors.lastname: Ozaki
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yamamoto
mesh_terms: 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
chemical_list: D002121:Calcium Channel Blockers; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D009020:Morphine; D004110:Diltiazem