PMID- 1278236
OWN - NLM
STAT- MEDLINE
DCOM- 19760901
LR  - 20190623
IS  - 0014-2999 (Print)
IS  - 0014-2999 (Linking)
VI  - 37
IP  - 1
DP  - 1976 May
TI  - Prevention and reversal of tolerance to barbiturates by intraventricular 
      injection of hemicholinium-3.
PG  - 125-32
AB  - Intracerebroventricular (i.c.v.) injection of phenobarbital, 800 mug, or 
      intraperitoneal (i.p.) injection of hexobarbital, 100 mg/kg, into rats resulted 
      in a loss of righting reflex lasting 15.4 +/- 0.2 min and 20.7 +/- 0.7 min, 
      respectively. A 40-60% reduction in this response was obtained following 
      administration of phenobarbital either i.c.v. (800 mug 4 times daily) or i.p. (80 
      mg/kg/day) for 4 days. Although these treatments also increased hepatic mixed 
      function oxidase activity, this enzyme induction was shown to be unrelated to the 
      development of tolerance to loss of righting reflex. I.c.v. injection of 
      hemicholinium-3 (HC-3) in doses which reduce brain acetylcholine levels (4-20 
      mug) profoundly affected tolerance to the central depressant effect of the 
      barbiturates. Thus, depending upon the time of administration, HC-3 either 
      retarded or prevented development of this tolerance. Moreover, if tolerance was 
      allowed to progress normally, administration of HC-3 on day 4 or 5 returned the 
      duration of the loss of righting reflex toward normal values. HC-3 did not 
      influence either the duration of this response in non-tolerant rats or the 
      induction of the hepatic mixed function oxidase activity. These results suggest 
      that brain ACh plays an important role in the development and maintenance of 
      tolerance to the central depressant effects of barbiturates.
FAU - Brezenoff, H E
AU  - Brezenoff HE
FAU - Mycek, M J
AU  - Mycek MJ
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (Barbiturates)
RN  - 312-45-8 (Hemicholinium 3)
RN  - AL8Z8K3P6S (Hexobarbital)
RN  - EC 1.- (Oxidoreductases, O-Demethylating)
RN  - YQE403BP4D (Phenobarbital)
SB  - IM
MH  - Animals
MH  - Barbiturates/*pharmacology
MH  - Drug Tolerance
MH  - Hemicholinium 3/administration & dosage/*pharmacology
MH  - Hexobarbital/pharmacology
MH  - Injections, Intraventricular
MH  - Liver/enzymology
MH  - Male
MH  - Orientation/drug effects
MH  - Oxidoreductases, O-Demethylating/metabolism
MH  - Phenobarbital/pharmacology
MH  - Rats
MH  - Reflex/drug effects
MH  - Time Factors
EDAT- 1976/05/01 00:00
MHDA- 1976/05/01 00:01
CRDT- 1976/05/01 00:00
PHST- 1976/05/01 00:00 [pubmed]
PHST- 1976/05/01 00:01 [medline]
PHST- 1976/05/01 00:00 [entrez]
AID - 0014-2999(76)90015-7 [pii]
AID - 10.1016/0014-2999(76)90015-7 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 1976 May;37(1):125-32. doi: 10.1016/0014-2999(76)90015-7.