Further modifications of the leads ((R)-(+)-hyoscyamine and (p-chloropheny1)propionic acid a-tropanyl ester), which show analgesic and nootropic activities as a consequence of increased central presynaptic ACh release, are reported. 2-Phenoxy- and 2-(pheny1thio)alkanoic acid esters showed the best results. Several members of these classes possess analgesic properties which are comparable to that of morphine and at the same time are able to reverse dicyclomine-induced amnesia. Confirmation was found that the mechanism of action is due to an increase in ACh release at central muscarinic synapses and that both auto- and heteroreceptors controlling ACh release are very likely involved. According to the results obtained with (E)-(+)-hyoscyamine, analgesic activity is stereochemistry dependent, since the R-(+)-enantiomers are always more efficacious than the corresponding S-(-)-ones. On the basis of their potency and acute toxicity, compounds (*)-28 (SM21) and (*)-42 (SM32) were selected for further study.

Presynaptic Cholinergic Modulators as Potent Cognition Enhancers and Analgesic Drugs. 2. 2-Phenoxy-, 2-(phenylthio)- and 2-(phenylamino)alkanoic Acid Esters / F. GUALTIERI; C. BOTTALICO; A. CALANDRELLA; S. DEI; M. GIOVANNONI; S. MEALLI; M. ROMANELLI; S. SCAPECCHI; E. TEODORI; N. GALEOTTI; C. GHELARDINI; A. GIOTTI; A. BARTOLINI. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - STAMPA. - 37:(1994), pp. 1712-1719. [10.1021/jm00037a023]

Presynaptic Cholinergic Modulators as Potent Cognition Enhancers and Analgesic Drugs. 2. 2-Phenoxy-, 2-(phenylthio)- and 2-(phenylamino)alkanoic Acid Esters

GUALTIERI, FULVIO;DEI, SILVIA;GIOVANNONI, MARIA PAOLA;ROMANELLI, MARIA NOVELLA;SCAPECCHI, SERENA;TEODORI, ELISABETTA;GALEOTTI, NICOLETTA;GHELARDINI, CARLA;GIOTTI, ALBERTO;BARTOLINI, ALESSANDRO
1994

Abstract

Further modifications of the leads ((R)-(+)-hyoscyamine and (p-chloropheny1)propionic acid a-tropanyl ester), which show analgesic and nootropic activities as a consequence of increased central presynaptic ACh release, are reported. 2-Phenoxy- and 2-(pheny1thio)alkanoic acid esters showed the best results. Several members of these classes possess analgesic properties which are comparable to that of morphine and at the same time are able to reverse dicyclomine-induced amnesia. Confirmation was found that the mechanism of action is due to an increase in ACh release at central muscarinic synapses and that both auto- and heteroreceptors controlling ACh release are very likely involved. According to the results obtained with (E)-(+)-hyoscyamine, analgesic activity is stereochemistry dependent, since the R-(+)-enantiomers are always more efficacious than the corresponding S-(-)-ones. On the basis of their potency and acute toxicity, compounds (*)-28 (SM21) and (*)-42 (SM32) were selected for further study.
1994
37
1712
1719
F. GUALTIERI; C. BOTTALICO; A. CALANDRELLA; S. DEI; M. GIOVANNONI; S. MEALLI; M. ROMANELLI; S. SCAPECCHI; E. TEODORI; N. GALEOTTI; C. GHELARDINI; A. ...espandi
File in questo prodotto:
File Dimensione Formato  
1.JMC.pdf

accesso aperto

Tipologia: Versione finale referata (Postprint, Accepted manuscript)
Licenza: Open Access
Dimensione 1.96 MB
Formato Adobe PDF
1.96 MB Adobe PDF

I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/309289
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 35
  • ???jsp.display-item.citation.isi??? 31
social impact