Alkaloids ofDelphinium speciosum
On separating the total alkaloids we isolated methyllycaconitine, lycoctonine, anthranoyllycoctonine, and gigactonine, which were identified on the basis of an analysis of spectral characteristics and a comparison of the I~C NMR spectra. In addition to these, a base was isolated with mp 180-182°C (acetone), composition C22H35N05 (I). The NMR spectrum of (I) had the signals of tertiary C-methyl group (0.97 ppm, 3 H, singlet), of a N-ethyl group (1.04 ppm, 3 H, triplet, J = 7 Hz), and of a methoxy group (3.82 ppm, 3 H, singlet), and also one-proton signals at 4.12 ppm (triplet, J = 5 Hz) and 4.6 ppm (doublet, J = 7 Hz), The IR spectrum showed the absorption bands of hydroxy groups at 3400-3600 cm -: and of ether bonds at ii00 cm -~. The mass spectrum of (I) was characteristic for alkaloids with the lycoctonine skeleton and was close to the spectrum of karakoline [2, 3]. The maximum peak in the mass spectrum of (I) was the peak of the M +17 ion, showing the presence of the hydroxy group at C-I [2], Acetylation of the alkaloid with acetic anhydride in the presence of pyridine yielded the triacetate (II) with mp 162-164°C (acetone), showing the presence of three secondary hydroxy groups. Its mass spectrum contained the peak of the molecular ion M + 519 (8%), and also the peaks of ions with m/z 476 (8%), 460 (100%), 416 (15%) and 400 (12%), The PMR spectrum contained the signals of a N-ethyl, a tertiary C-methyl, and of three acetoxy groups, and also one-proton signals at 4.68 ppm (triplet, J = 5 Hz), 4.75 ppm (quartet, ABX system, JAX = i0 Hz, JBX = 7 Hz) and 5.22 ppm (doublet, J = 7 Hz), showing the presence of hydroxy groups at C-14, C-I, and C-6 [3, 4]. The acetylation of (I) with acetyl chloride gave the tetraacetate (III). Its mass spectra contained the peak of the molecular ion M + 561 (1%), and also the peaks of ions with m/z 502 (77%), 442 (33%), 400 (100%), and 372 (33%), According to these results, the fourth hydroxy group must be located at C-8, The information obtained indicated that (I) was alkaloid B, isolated previously from Delphinium bicolor Nutt, [4-7]. A direct comparison with alkaloid B kindly supplied by Prof, M. N, Benn showed their identity.
The alkaloids of nutt.
The structures of alkaloid- and - were established via X-ray crystallography of the former as its HI salt, and its chemical conversion to the latter.
Pharmacokinetics and Metabolism of 14C-Brivaracetam, a Novel SV2A Ligand, in Healthy Subjects
This study was designed to investigate the human absorption, disposition, and mass balance of 14C-brivaracetam, a novel high affinity SV2A ligand with potent anticonvulsant activity. Six healthy male subjects received a single p.o. dose of 14C-brivaracetam (150 mg, 82 μCi, or 3.03 MBq). Serial blood and complete urine and feces were collected until 144 h postdose. Expired air samples were obtained until 24 h. Brivaracetam was rapidly absorbed, with Cmax of 4 μg/ml occurring within 1.5 h of dosing. Unchanged brivaracetam amounted to 90% of the total plasma radioactivity, suggesting a modest first-pass effect. Plasma protein binding of radioactivity was low (17.5%). Urinary excretion exceeded 90% after 2 days, and the final mass balance reached 96.8% of the radioactivity in urine and 0.7% in feces. Only 8.6% of the radioactive dose was recovered in urine as unchanged brivaracetam, the remainder being identified as non–cytochrome P450 (P450)- and P450-dependent biotransformation products resulting from hydrolysis of the amide moiety (M9, 34.2%), hydroxylation of the n-propyl side chain (M1b, 15.9%), and a combination of these two pathways leading to the hydroxy acid (M4b, 15.2%). Minor amounts of taurine and glucuronic acid conjugates and other oxidized derivatives were also identified. Brivaracetam is completely absorbed, is weakly bound to plasma proteins, extensively biotransformed through several metabolic pathways, and eliminated renally.