Diltiazem inhibits naloxone-precipitated and spontaneous morphine withdrawal in rats.
The effects of diltiazem, a Ca2+ channel blocker, on naloxone-precipitated and spontaneous morphine withdrawal were studied in male Sprague-Dawley rats. In naloxone-precipitated withdrawal, body weight loss and plasma corticosterone elevation were dose dependently inhibited by diltiazem injected 4 or 2 and 4 h before naloxone, respectively. Three administrations of diltiazem (17, 11 and 5 h before naloxone) did not reduce the above withdrawal signs. Diarrhea was dose dependently inhibited by all schedule of diltiazem treatments. In spontaneous withdrawal, body weight loss and plasma corticosterone elevation were dose dependently inhibited by two (6 and 12 h) or three (6, 12 and 18 h after the last morphine) treatments with diltiazem at 6-h intervals after the last morphine, but not by a single diltiazem injected 18 h after the last morphine.
Kishioka
S
S
Department of Pharmacology, Wakayama Medical College, Japan.
Inoue
N
N
Nishida
S
S
Fukunaga
Y
Y
Yamamoto
H
H
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003345:Corticosterone / Q000097:blood; D003967:Diarrhea / Q000139:chemically induced; D004110:Diltiazem / Q000494:pharmacology*; D004347:Drug Interactions; D008297:Male; D009020:Morphine / Q000009:adverse effects*; D009270:Naloxone / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009294:Narcotics / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013375:Substance Withdrawal Syndrome / Q000097:blood / Q000209:etiology*
D002121:Calcium Channel Blockers; D009292:Narcotic Antagonists; D009294:Narcotics; D009270:Naloxone; D009020:Morphine; D004110:Diltiazem; D003345:Corticosterone