Cytisine effects

Figure 14.10. "Binding data rat braid [ H]cytisine effective dose...

Genista tinctoria (dyer s broom) contains 0.3-0.8% of toxic quinolizidine alkaloids, such as anagyrin, cjhisine, and iV-methylcytisine. The last two constituents have peripheral effects similar to those of nicotine, whereas their central activity may be different. Anagjrine is a suspected animal teratogen and cytisine has teratogenic activity in rabbits. 

Varenicline, a small (molecular weight 211.27) achiral alkaloid, was identified in 1997 as a potential treatment for smoking cessation. Its selection as our clinical candidate came after years of effort to identify an effective and safe partial agonist selective for the a4(32 nAChR subtype. A majority of the analogs explored in the course of our work were structurally related to the natural product (-)-cytisine and variations thereof.The discovery synthesis shown in Scheme 3.1 is rooted in... 

Zachowski (104a) confirmed the reality of this respiratory stimulation in the cat, the mouse, and the rabbit. The cytisine is capable of ameliorating respiration depressed by morphine and acts reflexly via the carotid body. This author stated also that cocaine reinforces the circulatory effects of cytisine whereas ergotamine and yohimbine reduce them, thus proving the part played by the adrenergic stimulation. 

Cytisine is almost indistinguishable from nicotine in its pharmacological actions. On the uterus, little effect is noted on isolated preparations, but in vivo, cytisine induces strong contractions (118, 119). According to Dale and Laidlaw, the effect produced by cytisine in the cat depends on the sexual state of the animal. The uterus of the virgin animal is inhibited, whereas that of the pregnant cat is stimulated. Powerful contractions have been observed after the intravenous injection of 1.0 mg. in the gravid animal. 

Cytisine (12, 38). The ground tops and seeds of Laburnum vuLgare were air-dried and extracted in a soxhlet with 50 % aqueous ethanol to which had been added 2 % of acetic acid. The extract after concentration was cleared with lead acetate, concentrated, made alkaline with sodium hydroxide, and extracted six times with an equal volume of chloroform. This left only a trace of cytisine in the aqueous layer. When the chloroform was removed, the residual alkaloidal material crystallized in part. No clear-cut separation of components was accomplished by fractional crystallization of the free base or the crude picrate. The isolation of cytisine as the benzenesulfonyl derivative was effected according to the method of Ing (5), and benzenesulfonyl-cytisine was collected and recrystallized from ethanol as glistening prisms, m.p. 261 . Microchemical tests and picrate formation and identification were also used to establish the presence of cytisine in a particular plant. 

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