PMID- 3320347
OWN - NLM
STAT- MEDLINE
DCOM- 19880202
LR  - 20181130
IS  - 0022-3565 (Print)
IS  - 0022-3565 (Linking)
VI  - 243
IP  - 3
DP  - 1987 Dec
TI  - Tiletamine is a potent inhibitor of N-methyl-aspartate-induced depolarizations in 
      rat hippocampus and striatum.
PG  - 915-20
AB  - N-methyl-D,L-aspartate (NMA) antagonists are of potential value in the treatment 
      of epilepsy and ischemia, but commonly utilized compounds are of low potency and 
      poorly penetrate the brain. Tiletamine hydrochloride is a lipophilic and potent 
      veterinary anesthetic. This study shows tiletamine to be similar to ketamine and 
      to phencyclidine, agents known to interact with the NMA receptor. Effects of 
      tiletamine on synaptic transmission and on direct excitatory responses to 
      exogenous amino acids were examined in rat hippocampal and striatal slices. In 
      striatal slices, tiletamine inhibited the NMA-mediated, but not the spontaneous, 
      release of [3H]acetylcholine, with an IC50 of 70 nM. In hippocampal CA1 cells, 3 
      microM tiletamine in the perfusate reversibly blocked the intracellularly 
      recorded responses to ionophoretically applied NMA, but not to glutamate, 
      quisqualate and kainate. Tiletamine, 3 to 100 microM, had no effect on the 
      orthodromically elicited excitatory postsynaptic potential, action potential 
      amplitude or duration, resting membrane potential, or input resistance. In 
      Mg++-free perfusate, the excitatory postsynaptic potential was greatly augmented 
      to give a paroxysmal depolarization shift and was reversibly blocked by 10 microM 
      tiletamine. Our results show that tiletamine is a potent and reversible 
      antagonist of NMA-mediated responses without itself having major effects in low 
      concentrations on normal membrane and synaptic pyramidal cell properties.
FAU - ffRench-Mullen, J M
AU  - ffRench-Mullen JM
AD  - Department of Neurology, Johns Hopkins University, School of Medicine, Baltimore, 
      Maryland.
FAU - Lehmann, J
AU  - Lehmann J
FAU - Bohacek, R
AU  - Bohacek R
FAU - Fisher, R S
AU  - Fisher RS
LA  - eng
GR  - KO7-NS00697/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Pharmacol Exp Ther
JT  - The Journal of pharmacology and experimental therapeutics
JID - 0376362
RN  - 0 (Cyclohexanes)
RN  - 2YFC543249 (Tiletamine)
RN  - 30KYC7MIAI (Aspartic Acid)
RN  - 4368-28-9 (Tetrodotoxin)
RN  - 6384-92-5 (N-Methylaspartate)
RN  - I38ZP9992A (Magnesium)
RN  - N9YNS0M02X (Acetylcholine)
SB  - IM
MH  - Acetylcholine/metabolism
MH  - Action Potentials/drug effects
MH  - Animals
MH  - Aspartic Acid/*analogs & derivatives/antagonists & inhibitors
MH  - Corpus Striatum/*drug effects/physiology
MH  - Cyclohexanes/*pharmacology
MH  - Hippocampus/*drug effects/physiology
MH  - In Vitro Techniques
MH  - Magnesium/pharmacology
MH  - Male
MH  - N-Methylaspartate
MH  - Rats
MH  - Rats, Inbred Strains
MH  - Tetrodotoxin/pharmacology
MH  - Tiletamine/*pharmacology
EDAT- 1987/12/01 00:00
MHDA- 1987/12/01 00:01
CRDT- 1987/12/01 00:00
PHST- 1987/12/01 00:00 [pubmed]
PHST- 1987/12/01 00:01 [medline]
PHST- 1987/12/01 00:00 [entrez]
PST - ppublish
SO  - J Pharmacol Exp Ther. 1987 Dec;243(3):915-20.