Isocorydin

Dicentra canadensis Walp. Bulbocapnine, corydine, isocorydine, protopine. Base F 22, C3,H4oOiqN2, m.p. 237-8°, jdelds a quaternary chloride, C34H3oOgN2Cl(OMe)3, m.p. 286°. ... 

Isocorydine (1,2,10-trimethoxy-ll-hydroxyaporphine) was isolated for the first time by Maranon (422) and Go (423). Reynolds el al. (401) reported that its effect resembled that of bulbocapnine. Administration of N-methylisocorydinium chloride, a quaternary base isolated from Fagaro coco, results in apnea and finally in cardiac failure (424r-426). In rabbits it causes an increase in excitability whereas in rats it causes a decrease. The effect of mesantoine and coramine is to some extent antagonistic, which is contrary to the effect of lobeline and of the barbiturates. In rabbits and toads isocorydine diminishes the contractility and excitability of the skeletal muscles however, a curarelike effect was not observed. After intraperitoneal application to rats the recorded LD50 was 10.9 mg/kg. 

The alkaloids corydine, bulbocapnine, and isocorydine have an adrenolytic effect (427, 428). All of them, including glaucine, act cholinergically (429, 430) this effect is, however, smaller than that of dehydrocholic acid. For the synthesis and pharmacology of aporphine, the pharmacology of (— )-nornuciferine and of pukateine, see Kupchan, et al. (379), Weisbach et al. (431), and Smith et al. (432, 433), Burkman and Cannon (434), and Fogg (435). 

The following aporphine alkaloids were isolated anonaine, roeraerine, norcorydine, corydine, norisocorydine, isocorydine, and glaucine (7). 

Reticuline, laurotetanine, JWmethyllaurotetanine, isocorydine, and a new alkaloid, cryptodorine (C18H1504N [a] >9 +61° sulfate, mp 219-221°) were isolated. The latter on iV-methylation generated neolitsine hence, it has structure 68 (42). 

Isocorydine, as well as a number of bases previously reported, was isolated (119). 

In alkaloids such as isocorydine (57) and bulbocapnine (58), which contain substituents on C-10 and C-11, the chemical shifts of the ring D carbon atoms were determined not only by the methods discussed above but also by the observation of second-order effects in the off-resonance spectra of C-8 and... 

Apomorphine was the most potent of the protein kinase inhibitors (IC50 for PKA-catalytic subunit 1 pM). However, the methylated aporphine alkaloid analogues of apomorphine such as bulbocapnine, isocorydine, glaucine and (+)-boldine were either inactive or poor inhibitors of this en2 yme. 

The NMR-spectra of nuciferine, glaucine, A -methyllaurotetanine, dicentrine, ocoteine, corydine, isocorydine, bulhocapnine, and a variety of non-natural aporphines have been discussed in some detail 62). Trifluoroacetic acid or D20-Na0D may be used as solvent for those... 

Compound ii S -LVIII was synthesized by the Ullmann condensation of (— )-6 -bromolaudanosine (XL) with isocorydine (LVI) and was reported to be identical with thalicarpine. However, scrutiny of the spectral properties of thalicarpine showed that they are incompatible with structure i S-LVIII (32). For example, there is no AB quartet in the aromatic proton region of the NMR-spectrum of the alkaloid as would be expected of the neighboring aromatic protons in structure i (S-LVIII. Accordingly the condensation of compounds XL and LVI was reexamined and, as expected, the earlier result was not reproduced. 

T. aquilegifolium L., a species that grows in western Anatolia, is not a rich source of alkaloids, with only the monomeric aporphines magnoflorine, isoboldine, and isocorydine having been isolated. 

Fourteen alkaloids were isolated from extracts of the whole plant of ThaUctrum fauriei Hayata, among which were seven alkaloids of novel structure including three aporphines (3-0-demethyloconovine, faurine, and O-methylfaurine), three aporphine-benzylisoquinoline dimers (fauridine, faurithaline, and 3-methoxyfaurithaline), and one aporphine-pavine dimer (fauripavine). Alkaloids of previously established structure that were isolated and identified included five aporphines (corydine, isocorydine, isooconovine, oconovine, and thalisopynine), and two morphinans (ocobotrine and pallidine). 

Isocorydine was observed to significantly decrease the frequency of spontaneous contraction and muscle tension, but not the amplitude of contraction on the isolated isthmus of the oviduct of the rabbit The tension and frequency of spontaneous contraction was suppressed by the alkaloid at concentrations of 3-300 pmol/1, but the amplitude of contraction was decreased only at 300 pmol/1. The alkaloid antagonized the norepinephrine-induced contraction of the oviduct, and the transport of ova through the oviduct was delayed by isocorydine [285]. 

Isocorydine was observed to antagonize the contraction of isolated guinea pig or rabbit biliary tracts induced by acetylcholine, histamine, angiotensin II, and K+. The relaxant effect of the alkaloid on isolated gallbladder and the Sphincter of Oddi in vitro was similar to that observed with verapamil, thus suggesting that Ca+2 may be involved in the relaxant effect of isocorydine [286]. 

Standard microelectrode techniques were used to study the effects of isocorydine on potential characteristics of canine cardiac Purkinje fibers and ventricular myocardium in vitro. In the Purkinje fibers, the action potential durations APDjj and APD were prolonged at 3 pmol/1 but shortened at 30 pmol/1 by isocorydine. The action potential amplitude and maximal upstroke velocity were decreased at 100 pmol/1. In the ventricular myocardium, the action potential characteristics were changed by isocorydine at concentrations above 30 pmol/1. The APDJ0 was shortened, the APD90 was prolonged, and the maximal upstroke velocity was decreased at 30 pmol/1. The effective refractory period was prolonged by the alkaloid in Purkinje fibers and ventricular myocardium. These results indicated that the alkaloid may interfere with K+, Na+, and Ca+2 currents in myocardial cell membranes at different concentrations [287]. 

Isocorydine, a Chinese medicinal calcium antagonist, was found to decrease blood pressure and heart rate in anesthetized rabbits [288],... 

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