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This work was supported by Ministerio de Educacion y Ciencia (SAF2006-13391-C03-01), Universidad Rey Juan Carlos - Comunidad de Madrid (URJC-CM-2006-BIO-0604), and Comunidad de Madrid (S-SAL/0261/2006). The authors wish to thank Oscar Gutierrez (Servicio de Radiologia, Clinica Universitaria, Universidad Rey Juan Carlos) for technical radiological advice.

Analysis of institutional authors

Abalo, RCorresponding AuthorLopez-Miranda, VAuthorVera, GAuthorGonzalez, CAuthorCastillo, MAuthorFernandez-Pujol, RAuthorMartin, MiAuthor

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September 27, 2022
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Selective lack of tolerance to delayed gastric emptying after daily administration of WIN 55,212-2 in the rat

Publicated to:Neurogastroenterology And Motility. 21 (9): 1002-e80 - 2009-09-01 21(9), DOI: 10.1111/j.1365-2982.2009.01315.x

Authors: Abalo, R; Cabezos, P A; Lopez-Miranda, V; Vera, G; Gonzalez, C; Castillo, M; Fernandez-Pujol, R; Martin, M I

Affiliations

Univ Rey Juan Carlos, Fac Ciencias Salud, Dept Ciencias Salud 3, Madrid 28922, Spain - Author

Abstract

P>The use of cannabinoids to treat gastrointestinal (GI) motor disorders has considerable potential. However, it is not clear if tolerance to their actions develops peripherally, as it does centrally. The aim of this study was to examine the chronic effects of the cannabinoid agonist WIN 55,212-2 (WIN) on GI motility, as well as those in the central nervous and cardiovascular systems. WIN was administered for 14 days, at either non-psychoactive or psychoactive doses. Cardiovascular parameters were measured in anaesthetized rats, whereas central effects and alterations in GI motor function were assessed in conscious animals using the cannabinoid tetrad and non-invasive radiographic methods, respectively. Tests were performed after first (acute effects) and last (chronic effects) administration of WIN, and 1 week after discontinuing treatment (residual effects). Food intake and body weight were also recorded throughout treatment. Blood pressure and heart rate remained unchanged after acute or chronic administration of WIN. Central activity and GI motility were acutely depressed at psychoactive doses, whereas non-psychoactive doses only slightly reduced intestinal transit. Most effects were reduced after the last administration. However, delayed gastric emptying was not and could, at least partially, account for a concomitant reduction in food intake and body weight gain. The remaining effects of WIN administration in GI motility were blocked by the CB1 antagonist AM 251, which slightly accelerated motility when administered alone. No residual effects were found 1 week after discontinuing cannabinoid treatment. The different systems show differential sensitivity to cannabinoids and tolerance developed at different rates, with delayed gastric emptying being particularly resistant to attenuation upon chronic treatment.

Keywords

(3r)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone2,3 dihydro 5 methyl 3 (morpholinomethyl) 6 (1 naphthoyl)pyrrolo[1,2,3 de][1,4]benzoxazineAbdominal radiographyAcute drug administrationAm 251Animal experimentAnimalsArticleBenzoxazinesBlood pressureBody weightBrainCannabinoidCannabinoid 1 receptor antagonistCannabinoid modulationCannabinoidsCardiovascular parametersCardiovascular systemCardiovascular-systemCb1Central nervous systemChronic drug administrationControlled studyDelayed gastric emptyingDelta(9)-tetrahydrocannabinolDose-response relationship, drugDrug toleranceDrug withdrawalEatingFood intakeGastric emptyingGastrointestinal motilityGastrointestinal tractGastrointestinal transitGuinea-pig ileumHeart rateIntestinal motilityIntestine transit timeMaleMorpholinesMotor performanceMyenteric plexusNaphthalenesNon invasive measurementNonhumanPiperidinesPriority journalPyrazolesRadiologyRatRatsRats, wistarReceptor immunoreactivityReceptor, cannabinoid, cb1Stomach emptyingStomach functionStomach function disorderStomach motilityToleranceWeight gain

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Neurogastroenterology And Motility due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2009, it was in position 34/167, thus managing to position itself as a Q1 (Primer Cuartil), in the category Clinical Neurology.

From a relative perspective, and based on the normalized impact indicator calculated from the Field Citation Ratio (FCR) of the Dimensions source, it yields a value of: 4.18, which indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: Dimensions Aug 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-08-07, the following number of citations:

  • WoS: 32
  • Scopus: 35
  • Europe PMC: 25

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-08-07:

  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 36 (PlumX).

Leadership analysis of institutional authors

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author (Abalo Delgado, Raquel) and Last Author (Martín Claudio, María Isabel).

the author responsible for correspondence tasks has been Abalo Delgado, Raquel.