Structure and hypotensive activity relationships of tetrandrine derivatives in stroke-prone spontaneously hypertensive rats

Koichiro Kawashima, Terumasa Hayakawa, Yuko Miwa, Hisayo Oohata, Takeshi Suzuki, Kazuko Fujimoto, Tatsunori Ogino, Zhengxiong Chen (Masao Chin)

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Abstract

1. 1. Structure and hypotensive activity relationships of tetrandrine (TD), an alkaloid isolated from the Chinese herb Radix stephaniae tetrandrae and its derivatives were investigated in conscious stroke-prone spontaneously hypertensive rats (SHRSP). 2. 2. Derivatives substituted at the 7-O position with various types of alkyl group produced varying degrees of hypotensive effect. 3. 3. While the demethylated derivative, fangchinoline (FC), and its acetylated compound had no effect on blood pressure, 7-O-methyl FC (TD), and 7-O-ethyl and 7-O-isopropyl FC at oral doses of 25 and 50 mg/kg produced a gradual and sustained hypotensive effect without any significant effects on heart rate and plasma renin concentration. 4. 4. Substitution at the 7-O position with longer side chains such as n-propyl, n-butyl and n-pentyl groups reduced both the degree and duration of hypotensive activity. 5. 5. Substitution of N-methyl groups at the 2 and 2′ positions with quaternary ammonium or N-oxide attenuated the hypotensive activity. 6. 6. The results of this study suggest a possibility that 7-O-ethyl and 7-O-isopropyl derivatives as well as TD can be considered as potential antihypertensive drugs because of the gradual onset and long duration of their hypotensive action in SHRSP.

Original languageEnglish
Pages (from-to)343-347
Number of pages5
JournalGeneral Pharmacology
Volume21
Issue number3
DOIs
Publication statusPublished - 1990

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tetrandrine
Inbred SHR Rats
Structure-Activity Relationship
Stroke
Ammonium Compounds
Alkaloids
Renin
Oxides
Antihypertensive Agents
Heart Rate
Blood Pressure

ASJC Scopus subject areas

  • Pharmacology

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Structure and hypotensive activity relationships of tetrandrine derivatives in stroke-prone spontaneously hypertensive rats. / Kawashima, Koichiro; Hayakawa, Terumasa; Miwa, Yuko; Oohata, Hisayo; Suzuki, Takeshi; Fujimoto, Kazuko; Ogino, Tatsunori; Chen (Masao Chin), Zhengxiong.

In: General Pharmacology, Vol. 21, No. 3, 1990, p. 343-347.

Research output: Contribution to journalArticle

Kawashima, Koichiro ; Hayakawa, Terumasa ; Miwa, Yuko ; Oohata, Hisayo ; Suzuki, Takeshi ; Fujimoto, Kazuko ; Ogino, Tatsunori ; Chen (Masao Chin), Zhengxiong. / Structure and hypotensive activity relationships of tetrandrine derivatives in stroke-prone spontaneously hypertensive rats. In: General Pharmacology. 1990 ; Vol. 21, No. 3. pp. 343-347.
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