PMID- 2494045
OWN - NLM
STAT- MEDLINE
DCOM- 19890424
LR  - 20190813
IS  - 0013-9580 (Print)
IS  - 0013-9580 (Linking)
VI  - 30
IP  - 2
DP  - 1989 Mar-Apr
TI  - Mechanisms of tolerance to the anticonvulsant effects of acetazolamide in mice: 
      relation to the activity and amount of carbonic anhydrase in brain.
PG  - 208-16
AB  - The mechanism by which tolerance develops to the anticonvulsant effects of 
      acetazolamide (AZM) was investigated in Swiss-Webster mice. The effects of single 
      and six daily doses of 40 mg or 200 mg/kg AZM on electroshock seizure threshold 
      (EST), maximal electroshock (MES) seizure pattern, and on the activity and total 
      amount of carbonic anhydrase II (CAII) in various subcellular fractions (cytosol, 
      microsomes, and myelin) of cerebral cortex, cerebellum, and brainstem were 
      assessed. The activity of CAII was measured by microassay, and the total amount 
      was measured by immunoassay methods developed in this laboratory. From the 
      activity (units per microgram of protein) and total amount (nanograms per 
      microgram protein) data, the specific activity (units per nanogram CAII) of the 
      enzyme was calculated. With multiple doses, tolerance developed to both elevation 
      of the EST and modification of the MES pattern noted with single doses of AZM. 
      Accompanying the development of tolerance to the anticonvulsant effects of AZM 
      was an increase in both the activity and specific activity of CAII in the various 
      subcellular fractions and areas of the brain. The effects were dose dependent. 
      Tolerance to the EST-elevating effects of AZM correlated with increases in the 
      activity, total amount, and specific activity of CAII in the myelin fraction of 
      the cerebral cortex.(ABSTRACT TRUNCATED AT 250 WORDS)
FAU - Anderson, R E
AU  - Anderson RE
AD  - Department of Physiology, University of Utah School of Medicine, Salt Lake City 
      84108.
FAU - Chiu, P
AU  - Chiu P
FAU - Woodbury, D M
AU  - Woodbury DM
LA  - eng
GR  - IR01 NS 21834/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Epilepsia
JT  - Epilepsia
JID - 2983306R
RN  - 0 (Anticonvulsants)
RN  - EC 4.2.1.1 (Carbonic Anhydrases)
RN  - O3FX965V0I (Acetazolamide)
SB  - IM
MH  - Acetazolamide/administration & dosage/*pharmacology
MH  - Animals
MH  - Anticonvulsants/administration & dosage/*pharmacology
MH  - Brain/*enzymology
MH  - Carbonic Anhydrases/*analysis/metabolism
MH  - Drug Tolerance
MH  - Electroshock
MH  - Immunoassay
MH  - Mice
MH  - Seizures/enzymology/physiopathology
EDAT- 1989/03/01 00:00
MHDA- 1989/03/01 00:01
CRDT- 1989/03/01 00:00
PHST- 1989/03/01 00:00 [pubmed]
PHST- 1989/03/01 00:01 [medline]
PHST- 1989/03/01 00:00 [entrez]
AID - 10.1111/j.1528-1157.1989.tb05456.x [doi]
PST - ppublish
SO  - Epilepsia. 1989 Mar-Apr;30(2):208-16. doi: 10.1111/j.1528-1157.1989.tb05456.x.