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Dopamine agonist activity of EMD 23,448

Journal Article:

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:

Journal Article:

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}
}