Campus Access Only

All rights reserved. This publication is intended for use solely by faculty, students, and staff of University of the Pacific. No part of this publication may be reproduced, distributed, or transmitted in any form or by any means, now known or later developed, including but not limited to photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the author or the publisher.

Date of Award

1993

Document Type

Dissertation - Pacific Access Restricted

Degree Name

Doctor of Philosophy (Ph.D.)

Department

Pharmacy

First Advisor

Marvin H. Malone

First Committee Member

James W. Blankenship

Second Committee Member

Madhukar Chaubal

Third Committee Member

David S. Fries

Fourth Committee Member

Michael J. M[?]

Fifth Committee Member

Howard S. Runion

Abstract

Powdered aerial parts of the weed yellow starthistle (Centaurea solstitialis, Compositae) and the methanol extract, alkaloidal and fatty fractions of the methanol extract of the aerial parts, injected intraperitoneally, produced a highly significant hypothermia in conscious normal rats. Other significant symptomatology included sedation, decreases in spontaneous motor activity, depressed respiration, mydriasis, ear blanching, enophthalmos and anuria. Four sesquiterpene lactones of the guaianolide type (repin, solstitialin-A, janerin and cynaropicrin), constituents of yellow starthistle, showed similar activities in rats. The predominant effects were hypothermia, sedation and enophthalmos. Both repin and janerin, in equidoses of 3.1-31 mg/kg, produced similar profiles of generalized effects and hypothermia, whereas solstitialin-A and cynaropicrin did not show well-defined dose-response relationships. The lethal doses of the methanol extract, repin, solstitialin-A, janerin and cynaropicrin were 1000, 31, 310, 31 and 310 mg/kg, respectively. Studies were carried out to document the effects of various potential antagonists and agonists on the repin-induced hypothermic effect. Rats were pretreated intraperitoneally with atropine sulfate (10 and 20 mg/kg), atropine methylbromide (20 mg/kg), propranolol (10 and 20 mg/kg), metergoline (0.5 mg/kg), ketanserin tartrate (0.2 mg/kg), diphenhydramine HCl (10 mg/kg) and apomorphine HCl (0.5 mg/kg). No significant effects of pretreatment were evident up to 2 h but statistically significant partial reversals of repin-induced hypothermia by atropine sulfate (20 mg/kg), metergoline, ketanserin, diphenhydramine and apomorphine were observed beginning 3 h after repin injection. Propranolol pretreatment resulted in a significant potentiation of repin's hypothermic effect. The sleeping time in mice induced by intraperitoneal sodium pentobarbital was markedly potentiated by pretreatment with repin. Receptor binding studies showed that repin facilitated the binding of GABA$\sb{\rm A},$ bombesin and neuropeptide Y without any significant binding of repin to any of the 36 receptors and binding sites tested.

Pages

252

To access this thesis/dissertation you must have a valid pacific.edu email address and log-in to Scholarly Commons.

Find in PacificSearch Find in ProQuest

Share

COinS

If you are the author and would like to grant permission to make your work openly accessible, please email

 

Rights Statement

Rights Statement

In Copyright. URI: http://rightsstatements.org/vocab/InC/1.0/
This Item is protected by copyright and/or related rights. You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s).