Premium
Pharmacological studies on a new dihydrothienopyridine calcium antagonist, S‐312‐d: Therapeutic effects of s‐312‐d on cerebral metabolic impairment in stroke‐prone spontaneously hypertensive rats
Author(s) -
Matsunaga Kazuki,
Masui Masao,
Ueda Motohiko
Publication year - 1994
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430330103
Subject(s) - medicine , endocrinology , creatine , acetylcholine , cholinergic , chemistry , cerebral cortex , cortex (anatomy) , psychology , neuroscience
The therapeutic effects of S‐312‐d on cerebral metabolic impairment were investigated in the stroke‐prone spontaneously hypertensive rats (SHRSP) with apparent stroke symptoms. S‐312‐d was orally administered 10 mg/kg/day (25 μmol/kg/day) to the SHRSP group (SP‐312) for 3 weeks. Several stroke symptoms such as piloerection, hyperreactivity, and limb paralysis in SHRSP were markedly alleviated in SP‐312. Their body weight and food intake also increased. The hypotensive and positive chronotropic effects with S‐312‐d were recovered to pre‐drug levels at 24 h after daily administration. The increases of water, Na + and Ca 2+ and the decreases of K + and Mg 2+ in the cortex of SHRSP administered 1% gum arabic solution (SP‐cont) were significantly improved in SP‐312. The increases of glucose and lactate/pyruvate ratio in the cortex of SP‐cont were also significantly reduced in SP‐312, while the recoveries of the decreased ATP and creatine phosphate in the cortex of SP‐312 were slight. The cholinergic and monoaminergic neurotransmitters in the brain were generally decreased in SP‐cont. The decreased acetylcholine (ACh) and choline acetyltransferase activity (CAT) in the cortex of SP‐cont were significantly restored in SP‐312. In the cortex, the decreased dopamine (DA) in SP‐cont was significantly restored, while the decreased norepinephrine (NE) and 5‐hydroxytryptamine (5‐HT) in SP‐cont were only slightly recovered in SP‐312. However, the decreased NE and 5‐HT in SP‐cont showed marked recovery in the hippocampus of SP‐312. Many biochemical deteriorations in cerebral organs such as marked edema, increases of Na + and Ca + contents, and decreases of several neurotransmitters in symptomatic SHRSP, which had some characteristic symptoms of stroke, seemed to be improved by the several pharmacological effects resulting from Ca 2+ antagonistic effects of S‐312‐d. These data suggests that S‐312‐d can prevent the deteriorating metabolic changes in SHRSP following the cerebral stroke. © 1994 Wiley‐Liss, Inc.