PMID- 9262174
OWN - NLM
STAT- MEDLINE
DCOM- 19971001
LR  - 20190614
IS  - 0006-8993 (Print)
IS  - 0006-8993 (Linking)
VI  - 762
IP  - 1-2
DP  - 1997 Jul 11
TI  - Beneficial effects of TDN-345, a novel Ca2+ antagonist, on ischemic brain injury 
      and cerebral glucose metabolism in experimental animal models with 
      cerebrovascular lesions.
PG  - 203-10
AB  - The effects of TDN-345 on mortality and ischemic neurological deficit following 
      transient global cerebral ischemia in Mongolian gerbils and also the rate of 
      local cerebral glucose utilization (LCGU) in stroke-prone spontaneously 
      hypertensive rats (SHRSP) with cerebrovascular lesions were investigated. In 
      Mongolian gerbils, ischemia was produced by clamping the bilateral common carotid 
      arteries for 15 min. TDN-345 (0.1-1.0 mg/kg) dose-dependently decreased the 
      mortality and ischemic neurological deficit score when administered orally twice, 
      60 min before ischemia and 90 min after recirculation. Additionally, TDN-345 (0.2 
      or 1.0 mg/kg, p.o. once daily for 3 weeks after the onset of stroke) decreased 
      the mortality and recurrence of stroke in SHRSP. To determine the site of action 
      of TDN-345 in the brain, the rate of LCGU in various brain regions in SHRSP with 
      stroke was examined using a [14C]2-deoxy-D-glucose method. The rate of LCGU 
      decreased significantly in all the brain regions in SHRSP with stroke compared 
      with Wistar-Kyoto (WKY) control rats, whereas the reduction in the rate of LCGU 
      in SHRSP with stroke was prevented by TDN-345 treatment, especially in the 
      sensorimotor cortex and locus coeruleus. These results suggest that TDN-345 has 
      therapeutic efficacy in the treatment of cerebrovascular disease.
FAU - Nakayama, T
AU  - Nakayama T
AD  - Pharmaceutical Research Division, Takeda Chemical Industries, Ltd., Yodogawa-ku, 
      Osaka, Japan. Nakayama_Takahiro@takeda.co.jp
FAU - Nagisa, Y
AU  - Nagisa Y
FAU - Imamoto, T
AU  - Imamoto T
FAU - Nagai, Y
AU  - Nagai Y
LA  - eng
PT  - Journal Article
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Calcium Channel Blockers)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Spiro Compounds)
RN  - 0 (TDN 345)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - Brain/*blood supply/metabolism
MH  - Brain Ischemia/*drug therapy/metabolism
MH  - Calcium Channel Blockers/*pharmacology
MH  - Cerebrovascular Disorders/drug therapy/metabolism
MH  - Disease Models, Animal
MH  - Dose-Response Relationship, Drug
MH  - Gerbillinae
MH  - Glucose/*metabolism
MH  - Male
MH  - Neuroprotective Agents/pharmacology
MH  - Rats
MH  - Rats, Inbred SHR
MH  - Rats, Inbred WKY
MH  - Reperfusion Injury/*drug therapy/metabolism
MH  - Spiro Compounds/chemistry/*pharmacology
EDAT- 1997/07/11 00:00
MHDA- 1997/07/11 00:01
CRDT- 1997/07/11 00:00
PHST- 1997/07/11 00:00 [pubmed]
PHST- 1997/07/11 00:01 [medline]
PHST- 1997/07/11 00:00 [entrez]
AID - S0006-8993(97)00388-0 [pii]
AID - 10.1016/s0006-8993(97)00388-0 [doi]
PST - ppublish
SO  - Brain Res. 1997 Jul 11;762(1-2):203-10. doi: 10.1016/s0006-8993(97)00388-0.