Corynanthine

Naunyn-schmiedeberg's Archives of Pharmacology, 01 Feb 1984, 325(2):136-144.

Comparison of the alpha-adrenoceptor antagonist profiles of idazoxan (RX 781094), yohimbine, rauwolscine and corynanthine.[Reference: WebLink]

In the present studies the potency and selectivity of idazoxan (RX 781094) were compared with yohimbine and its diastereoisomers rauwolscine and Corynanthine in both functional studies and radioligand binding experiments.
METHODS AND RESULTS:
Prejunctional alpha 2- and postjunctional alpha 1-adrenoceptor antagonist potencies were assessed by determining pA2 values against clonidine on the stimulated rat was deferens and noradrenaline on the anococcygeus muscle, respectively. The rank order of prejunctional alpha 2-adrenoceptor antagonist potency was idazoxan greater than yohimbine greater than rauwolscine much greater than Corynanthine. At postjunctional alpha 1-adrenoceptors the rank order of antagonist potency was rauwolscine greater than Corynanthine greater than yohimbine greater than idazoxan. The selectivity values (alpha 2/alpha 1) for idazoxan, yohimbine, rauwolscine and Corynanthine were 245, 45, 3 and 0.03 respectively. The selectivity and potency profiles established for these antagonists in functional studies were confirmed in radioligand binding studies utilising 3H-idazoxan (alpha 2) and 3H-prazosin (alpha 1) in rat cerebral cortex. In pithed rats intravenously administered idazoxan, yohimbine and rauwolscine fully reversed the inhibitory effects of clonidine on electrically-induced contractions of the vas deferens; idazoxan was approximately ten times more potent than both yohimbine and rauwolscine. Corynanthine was inactive. Idazoxan and yohimbine also fully antagonised the inhibitory effects of guanabenz on electrically-induced contractions of the anococcygeus muscle; idazoxan again was more than ten times more potent than yohimbine in this model.
CONCLUSIONS:
The inhibitory effects of guanabenz were less readily antagonised by rauwolscine indicating that the selectivity of this compound is less than that of yohimbine in this tissue. Corynanthine was again inactive.

International Journal of Immunopathology & Pharmacology, 1996, 9(2):59-65.

Reduction of mitogen-induced responsiveness of human and murine leukocytes in vitro by yohimbine and corynanthine.[Reference: WebLink]

This work was undertaken to assess the effects of yohimbine and Corynanthine firstly on the in vitro proliferation of human peripheral blood lymphocytes stimulated with various concentrations of phytohemagglutinin (PHA), concanavalin A (Con A) and pokeweed mitogen (PWM).
METHODS AND RESULTS:
Mononuclear cells were cultured in flat-bottomed 96-well microplates at 37°C for 96 (PHA and Con A) or 144 hours (PWM) in the presence of one mitogen and of one alkaloid. Concentrations of yohimbine and Corynanthine tested in cultures were 15 to 60 μg/ml and 30 to 120 μg/ml, respectively. Cell growth was measured by the incorporation of tritiated thymidine into lymphocyte DNA. We observed that both alkaloids inhibited lymphocyte DNA-synthesis in response to all mitogens. However, the effects were less pronounced when PWM was the lymphocyte stimulator, indicating that B cells are less susceptible to the drugs. Furthermore, yohimbine caused a greater inhibition than Corynanthine for a given concentration of the drugs. The alkaloids were added to cultures at different times after the beginning of the incubation period. The effect of Corynanthine occurred when the alkaloid was added during the first 24 hours of the cultures, whereas the effect of yohimbine was evident even 48 hours after addition to PHA- and Con A-stimulated lymphocyte cultures. We also tested the influence of both alkaloids (30 to 120 μg/ml) on the in vitro proliferation of murine spleen cells treated with 1% PHA and 50 μg/ml Con A and interleukin 2 (IL-2) secretion. In this case cell proliferation was assessed by the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) method and IL-2 production was analysed by ELISA. Similarly to what was observed with human peripheral lymphocytes, Corynanthine and yohimbine also inhibited murine leukocyte reactivity. Furthermore, the inhibition caused by the drugs was simultaneous to a suppression of IL-2 production.
CONCLUSIONS:
The present study therefore demonstrates that the stereoisomers indole alkaloids yohimbine and Corynanthine modulate DNA synthesis in mitogen-stimulated human lymphocytes.

Journal of Autonomic Pharmacology, 1995, 15(2):85-91.

Corynanthine inhibits, while idazoxan potentiates, cardiotoxic effects of ouabain.[Reference: WebLink]

1. Ouabain, infused intravenously to anaesthetized guinea-pigs induced ventricular premature beats, ventricular tachyarrhythmias and lethality.
METHODS AND RESULTS:
2. Corynanthine (1, 2 and 4 mg kg-1), an alpha 1-adrenoceptor antagonist and idazoxan (100, 200 and 400 micrograms kg-1), an alpha 2-adrenoceptor antagonist were administered 10 min prior to ouabain. Corynanthine (2 and 4 micrograms kg-1) showed significant increase in the amount of ouabain required to cause arrhythmia and lethality, whereas idazoxan (200 and 400 micrograms kg-1) decreased it. 3. Corynanthine inhibited the ouabain-induced pressor response while idazoxan potentiated it.
CONCLUSIONS:
4. Effects of these agents on the sympathetic nervous system appear to have played a significant role in its anti- and proarrhythmic actions.