PMID- 1329765
OWN - NLM
STAT- MEDLINE
DCOM- 19921118
LR  - 20190623
IS  - 0006-2952 (Print)
IS  - 0006-2952 (Linking)
VI  - 44
IP  - 7
DP  - 1992 Oct 6
TI  - Temperature and anion dependence of allosteric interactions at the 
      gamma-aminobutyric acid-benzodiazepine receptor.
PG  - 1297-302
AB  - The temperature dependence of [3H]flunitrazepam ([3H]FNZ) binding to rat brain 
      membranes was examined in the presence of the anaesthetics, pentobarbitone, 
      alphaxalone and propofol. Van't Hoff plots showed the binding of FNZ to be 
      largely enthalpy driven. Alphaxalone and propofol increased the entropy of the 
      binding reaction but not the enthalpy and therefore did not show temperature 
      dependence in their efficacy. In contrast, pentobarbitone increased the enthalpy 
      of FNZ binding and, therefore, is more efficacious at low temperatures. The EC50 
      values of all three modulators increased with temperature indicating that their 
      interactions with the receptor may be enthalpy driven. The EC50 values of all 
      three modulators were also anion dependent, showing a decrease in the presence of 
      gamma-aminobutyric acid (GABAA)-channel permeant anions. The efficacies of 
      alphaxalone and pentobarbitone, but not that of propofol, also increased with 
      increasing chloride ion concentration. The results indicate that all three 
      modulators interact with the GABAA receptor at distinct recognition sites.
FAU - Prince, R J
AU  - Prince RJ
AD  - Department of Pharmacology, School of Pharmacy, University of London, U.K.
FAU - Simmonds, M A
AU  - Simmonds MA
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (Anions)
RN  - 0 (Pregnanediones)
RN  - 0 (Receptors, GABA-A)
RN  - 620X0222FQ (Flunitrazepam)
RN  - BD07M97B2A (alphaxalone)
RN  - I4744080IR (Pentobarbital)
RN  - YI7VU623SF (Propofol)
SB  - IM
MH  - Animals
MH  - Anions
MH  - Binding, Competitive
MH  - *Brain Chemistry
MH  - Drug Interactions
MH  - Flunitrazepam/metabolism/*pharmacology
MH  - Male
MH  - Pentobarbital/pharmacology
MH  - Pregnanediones/pharmacology
MH  - Propofol/pharmacology
MH  - Rats
MH  - Rats, Wistar
MH  - Receptors, GABA-A/*drug effects/metabolism
MH  - Temperature
EDAT- 1992/10/06 00:00
MHDA- 1992/10/06 00:01
CRDT- 1992/10/06 00:00
PHST- 1992/10/06 00:00 [pubmed]
PHST- 1992/10/06 00:01 [medline]
PHST- 1992/10/06 00:00 [entrez]
AID - 0006-2952(92)90529-R [pii]
AID - 10.1016/0006-2952(92)90529-r [doi]
PST - ppublish
SO  - Biochem Pharmacol. 1992 Oct 6;44(7):1297-302. doi: 10.1016/0006-2952(92)90529-r.