Novel short-acting non-depolarizing muscle relaxants derived from galantamine : design, synthesis, and pharmacological evaluation

Frangež, Robert (avtor), Rouleau, Julien (avtor), Molgó, Jordi (avtor), Žužek, Monika C. (avtor), Benoit, Evelyne (avtor), Guillou, Catherine (avtor)

This study evaluated two novel galantamine-derived compounds, DR-976 and compound 15, as potential short-acting, non-depolarizing muscle relaxants. The aim was to introduce a long carbon chain bearing a quaternary ammonium group on the galantamine scaffold, in order to redirect its pharmacological profile from allosteric potentiating activity toward neuromuscular blocking effect. The compound effects were compared with those of d-tubocurarine (dTC), the classical competitive antagonist of nicotinic acetylcholine receptors (nAChRs). In anesthetized rats, both compounds produced dose-dependent inhibition of nerve-evoked skeletal muscle twitches, with mean effective doses (ED₅₀) of 0.57 mg/kg for DR-976 and 1.25 mg/kg for compound 15, compared with 0.07 mg/kg for dTC. Recovery of twitch amplitude was significantly faster for DR-976 and compound 15, with mean total recovery times of about 17 and 5 min, respectively, versus 34 min for dTC. Neither compound produced significant changes in arterial blood pressure, heart rate, electrocardiogram, or serum electrolytes, even at high doses. In vitro studies using isolated mouse phrenic nerve-hemidiaphragm preparations confirmed that DR-976, the most potent muscle relaxant, acts as a competitive antagonist at muscle-type nAChRs, with a mean inhibitory concentration (IC₅₀) of 1.45 µM, closely matching that of dTC (1.57 µM). These results demonstrate that DR-976 and compound 15 are short-acting, non-depolarizing neuromuscular blockers with rapid reversibility and excellent cardiovascular safety. Their competitive antagonism at muscle-type nAChRs, combined with short duration and hemodynamic stability, highlights their potential as next-generation muscle relaxants for short surgical, diagnostic, or emergency procedures where rapid recovery is desired.

• Jezik: Angleški jezik
• Ključne besede: galantamine derivatives, muscle relaxants, nicotinic acetylcholine receptors, rodent neuromuscular transmission, electrophysiology, cardiovascular system, serum electrolytes
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: VF - Veterinarska fakulteta
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2026
• Št. strani: 11 str.
• Številčenje: Vol. 196, art. 119099
• PID: 20.500.12556/RUL-183041
• UDK: 615.212:615.014:547.92
• ISSN pri članku: 1950-6007
• DOI: 10.1016/j.biopha.2026.119099
• COBISS.SI-ID: 267994883
• Datum objave v RUL: 03.06.2026

Gradivo je del revije

• Naslov: Biomedicine & pharmacotherapy
• Skrajšan naslov: Biomed. pharmacother.
• Založnik: Éditions scientifiques et médicales Elsevier
• ISSN: 1950-6007
• COBISS.SI-ID: 23136261

Licence

• Licenca: CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by/4.0/deed.sl
• Opis: To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: derivati ​​galantamina, mišični relaksanti, nikotinski acetilholinski receptorji, nevromuskularni prenos pri glodalcih, elektrofiziologija, kardiovaskularni sistem, serumski elektroliti

Projekti

• Financer: ARIS - Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije
• Številka projekta: P4-0053-2019
• Naslov: Endokrini, imunski in encimski odzivi pri zdravih in bolnih živalih

• Financer: Drugi - Drug financer ali več financerjev
• Številka projekta: BI-FR-21-22-PROTEUS-002/46143VH
• Naslov: Bilateral Slovenian/French Proteus Program