You need JavaScript to view this

Dopamine agonist activity of EMD 23,448

Abstract

EMD 23,448 was examined in tests of dopaminergic function and was found to be an atypical dopamine (DA) agonist. EMD 23,448 was a weak or inactive DA agonist when examined in tests of normal postsynaptic DA receptor function: production of stereotypy in the rat (ED/sub 50/ greater than sign 5.0 mg/kg.i.p.); production of emesis in beagles (minimum effective dose = 81..mu..g/kg i.v.); and, enhanced locomotor activity of the mouse (no excitation in doses <=50 mg/i.p.). Moreover, EMD 23,448 was relatively weak in competing for (/sup 3/H)-apomorphine binding to rat striatal membranes (Ki, 205 nM). On the other hand, this indolyl-3-butylamine did activate supersensitive postsynaptic DA receptors. Specifically, it elicited contralateral turning in rats with a unilateral 6-hydroxydopamine lesion of the substantia nigra (ED/sub 50/ value = 0.9 mg/kg) and did elicit stereotypy in rats given chronic daily haloperidol treatments. EMD 23,448 also exerted pharmacological effects in tests designed to measure activation of dopamine autoreceptors. It inhibited the ..gamma..-butyrolactone-induced increase in striatal dopa levels (ED/sub 50/ = 1 mg/kg i.p.) and produced a dose-related fall in the locomotor activity of the mouse. The results are discussed and contrasted with data derived for apomorphine and the putatively selective autoreceptor agonist (+-)-3-PPP.
Authors:
Martin, G E; Pettibone, D J [1] 
  1. Merck Sharp and Dohme Research Laboratories, West Point, Pennsylvania (USA). Dept. of Pharmacology
Publication Date:
Jan 01, 1985
Product Type:
Journal Article
Reference Number:
AIX-16-057774; EDB-85-142140
Resource Relation:
Journal Name: J. Neural Transm.; (Austria); Journal Volume: 61:1/2
Subject:
59 BASIC BIOLOGICAL SCIENCES; DOPAMINE; RADIORECEPTOR ASSAY; LABELLED COMPOUNDS; RATS; RECEPTORS; TRITIUM; AMINES; ANIMALS; AROMATICS; AUTONOMIC NERVOUS SYSTEM AGENTS; BETA DECAY RADIOISOTOPES; BETA-MINUS DECAY RADIOISOTOPES; CARDIOTONICS; CARDIOVASCULAR AGENTS; DRUGS; HYDROGEN ISOTOPES; HYDROXY COMPOUNDS; ISOTOPE APPLICATIONS; ISOTOPES; LIGHT NUCLEI; MAMMALS; NEUROREGULATORS; NUCLEI; ODD-EVEN NUCLEI; ORGANIC COMPOUNDS; PHENOLS; POLYPHENOLS; RADIOISOTOPES; RODENTS; SYMPATHOMIMETICS; TRACER TECHNIQUES; VERTEBRATES; YEARS LIVING RADIOISOTOPES; 551001* - Physiological Systems- Tracer Techniques
OSTI ID:
5436970
Country of Origin:
Austria
Language:
English
Other Identifying Numbers:
Journal ID: CODEN: JNTMA
Submitting Site:
HEDB
Size:
Pages: 115-123
Announcement Date:

Citation Formats

Martin, G E, and Pettibone, D J. Dopamine agonist activity of EMD 23,448. Austria: N. p., 1985. Web. doi:10.1007/BF01253056.
Martin, G E, & Pettibone, D J. Dopamine agonist activity of EMD 23,448. Austria. doi:10.1007/BF01253056.
Martin, G E, and Pettibone, D J. 1985. "Dopamine agonist activity of EMD 23,448." Austria. doi:10.1007/BF01253056. https://www.osti.gov/servlets/purl/10.1007/BF01253056.
@misc{etde_5436970,
title = {Dopamine agonist activity of EMD 23,448}
author = {Martin, G E, and Pettibone, D J}
abstractNote = {EMD 23,448 was examined in tests of dopaminergic function and was found to be an atypical dopamine (DA) agonist. EMD 23,448 was a weak or inactive DA agonist when examined in tests of normal postsynaptic DA receptor function: production of stereotypy in the rat (ED/sub 50/ greater than sign 5.0 mg/kg.i.p.); production of emesis in beagles (minimum effective dose = 81..mu..g/kg i.v.); and, enhanced locomotor activity of the mouse (no excitation in doses <=50 mg/i.p.). Moreover, EMD 23,448 was relatively weak in competing for (/sup 3/H)-apomorphine binding to rat striatal membranes (Ki, 205 nM). On the other hand, this indolyl-3-butylamine did activate supersensitive postsynaptic DA receptors. Specifically, it elicited contralateral turning in rats with a unilateral 6-hydroxydopamine lesion of the substantia nigra (ED/sub 50/ value = 0.9 mg/kg) and did elicit stereotypy in rats given chronic daily haloperidol treatments. EMD 23,448 also exerted pharmacological effects in tests designed to measure activation of dopamine autoreceptors. It inhibited the ..gamma..-butyrolactone-induced increase in striatal dopa levels (ED/sub 50/ = 1 mg/kg i.p.) and produced a dose-related fall in the locomotor activity of the mouse. The results are discussed and contrasted with data derived for apomorphine and the putatively selective autoreceptor agonist (+-)-3-PPP.}
doi = {10.1007/BF01253056}
journal = {J. Neural Transm.; (Austria)}
volume = {61:1/2}
journal type = {AC}
place = {Austria}
year = {1985}
month = {Jan}
}