Cyclic antidepressant overdose is a major cause of morbidity and mortality in self-poisoned patients. The major cause of mortality with cyclic antidepressant overdose is cardiotoxicity. We determined plasma catecholamine levels in 41 symptomatic acute overdose patients to identify interactions between QRS duration (a marker for cardiotoxicity) and a presumed hyper-adrenergic state. Using a linear multivariable regression analysis, QRS duration correlated with the presence of cyclic antidepressant, plasma norepinephrine levels, the ratio of norepinephrine to epinephrine level, and pulse rate (p less than 0.001, r2 = 0.42). Commensurate physiologic changes were not found in the presence of elevated catecholamine levels in the cyclic antidepressant overdose group. One possible explanation for the blunted systemic response to the elevated catecholamine levels is adrenergic desensitization. Investigation of serial catecholamine levels during cyclic antidepressant overdose may lead to modification of our current theories of cardiotoxicity and therapy.
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http://dx.doi.org/10.3109/15563659109038610 | DOI Listing |
Org Lett
January 2025
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, China.
Here, we report on methods for late-stage peptide diversification through palladium-catalyzed site-selective C(sp)-H amination of tryptophan residues at the C4 position, utilizing tryptophan-amine cross-links. Our strategy enables practical access to C-N bonds, facilitating the construction of cyclopeptides via late-stage cyclodimerization of structurally complex peptides, which poses significant challenges for organic synthesis. The synthetic utility of this protocol is demonstrated through the synthesis of 30- to 38-membered macrocyclic peptides.
View Article and Find Full Text PDFOrg Lett
January 2025
Department of Chemistry, University of Waterloo, 200 University Ave. West, Waterloo, Ontario, Canada N2L3G1.
The first total synthesis of cyclic depsipeptide antibiotic LL-A0341β (LL) is described. The configuration of the β-methyltryptophan (β-MeTrp) residue was established by preparing all four stereoisomers of Fmoc-β-MeTrp which were used for the synthesis of LL via Fmoc solid phase peptide synthesis. The most active of the four peptides was the one containing (2,3)-β-MeTrp.
View Article and Find Full Text PDFJ Org Chem
January 2025
Department of Organic and Medicinal Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Isoprenylation of the indole C3-position of tryptophan accompanied by cyclization (c-Trp) is one of the most attractive post-translational modifications because of C-C bond formation and drastic conformational alteration. As the modification generates two stereoisomers of the 6/5/5-fused ring system and consequently, a mixture of four possible conformations as considered in proline, it is expected to influence the biological activity in quorum sensing pheromone ComX containing the c-Trp residue. In this study, the simultaneous control of the amide equilibrium and pyrrolidine ring puckering was achieved by utilizing an N-carbamoylated and α-methylated 6/5/5-fused ring system.
View Article and Find Full Text PDFClin Chim Acta
February 2025
Student Research Committee, Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:
Electrochemical biosensors have revolutionized the detection of biomarkers related to depression and the quantification of antidepressant drugs. These biosensors leverage nanomaterials and advanced assay designs to achieve high sensitivity and selectivity for clinically relevant analytes. Key neurotransmitters implicated in depression, such as serotonin, dopamine, and glutamate, can be accurately measured via biosensors, providing insights into the effects of antidepressant treatments on neurotransmission.
View Article and Find Full Text PDFOrg Lett
December 2024
School of Chemistry, The University of Sydney, Sydney, NSW 2006, Australia.
The rufomycins are a family of nonribosomal cyclic peptides isolated from the deep sea-dwelling Herein, we describe the total synthesis of six congeners in the rufomycin family. Synthesis was achieved through a modular solid-phase strategy, incorporating synthetic nonproteinogenic amino acids: l-2-amino-4-hexenoic acid, prenyl-l-tryptophan (and related ()-epoxide), and -methyl-δ-hydroxy-l-leucine. Following macrolactamization, these peptides were further diversified through late-stage oxidation and secondary cyclization to furnish a library of six synthetic natural products.
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