A Pharmacological Study of Two Bisbenzylisoquinoline Alkaloids, Thalistyline and Obamegine

Abstract

Thalistyline, a monoquaternary bisbenzylisoquinoline alkaloid isolated from Thalictrum sp. inhibited respiration in anesthetized dogs. Thalistyline is about one-fourth as potent as d-tubocurarine in blocking neuromuscular transmission in the rat hemidiaphragm preparation. The pharmacological mechanism of action of the alkaloid is similar to that of d-tubocurarine. Obamegine did not exhibit curare-like activity. On the isolated rabbit aorta, contractions induced by an alpha-adrenoreceptor agonist, phenylephrine, were antagonized by both alkaloids. Increasing concentrations of thalistyline produced parallel shifts to the right in the dose-response curves of phenylephrine. The pA2 value for the competitive pharmacological antagonism was 6.33. Obamegine also antagonized the effects of phenylephrine on the aorta, line and obamegine lowered blood pressure in normotensive dogs. The effect was transient. Repeated injections of the alkaloids resulted in tachyphylaxis to blood pressure lowering effects. Although alkaloids exhibited alpha adrenergic blockade in the vascular preparation, the mechanism for the hypotensive effect remains to be established.

Bisbenzylisoquinoline Alkaloids

“…The alkaloid antagonized the phenylephrine-induced contractions of aortic strips (rabbit) and, thus, possessed a-adrenoreceptor blocking activity. There was no effect on canine respiration, nor was there inhibition of neuromuscular transmission (1-30X 10-6M) (27).…”

“…Phenylephrine-induced contractions of the aorta (rabbit) were antagonized with increasing concentrations of the alkaloid, producing parallel shifts to the right in phenylephrine dose-response curves. An a-adrenergic blockade in the vascular preparation is evident, but the hypotensive mechanism remains to be established (27).…”

“…ArH 5.97 (H-8'), 6.46 (dd)(lH)(7= 1.9, 8.2 Hz)(H-10'), 6.55 (H-5), 6.61 (d)(lH)(7= 1.8 Hz)(H-10), 6.69(H-5'), 6.66-6.73 (m)(2H)( -11' andH-13'), 6.82 (d)(1H)(7= 8.3 Hz)(H-13), 6.96 (dd) (1H) (7= 1.8, 8.3 Hz) (H-14), 7.11 (dd) (1H) (7=1.9, 8.2 Hz) (H-14') (193) 152 COCSOLINE (C34H3205N2: 548.2311) MS: M+548 (57), 547 (57), 349 (4), 335 (100), 334 (27), 321 (26), 305 (13), 168(6), 107 (4) (175) CD: Negative tail 0(215), +32 (229), 0 (251), +1(252), +9 (290), 0 (315) (175) 153 COCSULINE (C35H3405N2: 562.2468) CD: +44(239), +11 (292) (122) Negative tail, 0(214), +27 (232), +2(250), +7.3 (292), 0 (320) (175) 157 ISOTRILOBINE (C36H3605N2: 576.2624) UV: 234(4.56), 287 (3.65) (175) MS: M+576 (22), 575 (15), 349 (100), 335 (44), 319 (7), 175 (59) (175) CD: Negative tail, 0(213), +31(234), +2(251), +8(290), 0(320) (175) 161 TRICORDATINE (C34H3205N2: 548.2311) CD: Negative tail, 0 (218), +9 (234), 0 (255), +2.3 (sh) (270), +2.5 (290), 0 (310) (175) 168 REPANDULINE (C37H3607N2:620.2523) nmr: NCH3 2.40 (N-2), 2.65 (N-2'), OCH3 3.62, CH202 5.92 +5.97, A1H 2.9-3.0 (H-l), 2.9-3.05 (H-3eq), 2.4-2.6 (H-3ax), 1.95-2.15 (H-4eq), 2.3-2.5 (H-4ax), 4.15 (HA), 3.88 (HB), 2.95-3.10 ( -), 2.90-3.05 (H-a), 3.30-3.38 (H-a'), 2.63-2.73 (H-a'),…”

Natural Agents and Extracts

“…Neferine (see 5) a dimeric benzyltetrahydroisoquinoline alkaloid from the embryos of the Indian lotus, Nelumbo nucifera (Nympheaceae), exhibits antihypertensive activity in anesthetized SHR ). 5 2.5.2 Thalystyline and Obamegine Thalystyline (see 6), a monoquarternary bisbenzylisoquinoline alkaloid, and obamegine (see 7), a similar structure but lacking quarternary nitrogen, were both isolated from Thalictrum species (BANNING et al 1982). They lower blood pressure in normotensive dogs.…”

Separation of bisbenzylisoquinoline alkaloids by micellar electrokinetic chromatography

“…Bisbenzylisoquinoline alkaloids, which occur primarily in the Berberidaceae, Menispermaceae, Monimiaceae and Ranunculaceae (Schiff, 1983) and recently found in the Lauraceae (Chen, 1996), are reported to have various pharmacological characteristics such as calcium antagonistic (Cha et al, 1983), anti-arrhythmic (Ke et al, 1981), platelet aggregation inhibiting (Qian and Huang, 1989), adrenoblocking (Bonning et al, 1982), histamine release inhibiting (Nakamura et al, 1992), immunosuppressive (Kondo et al, 1992) and anti-plasmodial (Marshall et al, 1994;Angerhofer et al, 1999) activities.…”