Anthracene-Walled Acyclic CB[n] Receptors: inâ
vitro and inâ
vivo Binding Properties toward Drugs of Abuse.
ChemMedChem
; 17(10): e202200046, 2022 05 18.
Article
en En
| MEDLINE
| ID: mdl-35238177
ABSTRACT
We report studies of the interaction of six acyclic CB[n]-type receptors toward a panel of drugs of abuse by a combination of isothermal titration calorimetry and 1 H NMR spectroscopy. Anthracene walled acyclic CB[n] host (M3) displays highest binding affinity toward methamphetamine (Kd =15â
nM) and fentanyl (Kd =4â
nM). Host M3 is well tolerated by Hep G2 and HEK 293 cells up to 100â
µM according to MTS metabolic and adenylate kinase release assays. An inâ
vivo maximum tolerated dose study with Swiss Webster mice showed no adverse effects at the highest dose studied (44.7â
mg kg-1 ). Host M3 is not mutagenic based on the Ames fluctuation test and does not inhibit the hERG ion channel. In vivo efficacy studies showed that pretreatment of mice with M3 significantly reduces the hyperlocomotion after treatment with methamphetamine, but M3 does not function similarly when administered 30 seconds after methamphetamine.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Metanfetamina
Límite:
Animals
/
Humans
Idioma:
En
Revista:
ChemMedChem
Asunto de la revista:
FARMACOLOGIA
/
QUIMICA
Año:
2022
Tipo del documento:
Article
País de afiliación:
Estados Unidos