Journal article
Dopaminergic structure-activity relationships of 2-aminoindans and cardiovascular action and dopaminergic activity of 4-hydroxy, 5-methyl, 2-di-n-propylaminoindan (RD-211)
The Journal of pharmacology and experimental therapeutics, Vol.256(2), pp.751-756
02/1991
DOI: 10.1016/S0022-3565(25)22981-0
PMID: 1671601
Abstract
Dopaminergic structure-activity relationships of 2-aminoindans were evaluated for their ability to inhibit responses to stimulation of cardioaccelerator nerves in cats. The major observations were as follows: 1) Unsubstituted di-n-propyl- and diethyl 2-aminoindan derivatives do not inhibit responses to stimulation of cardioaccelerator nerve, although previous studies identified stimulation of DA2-receptors. 2) 4-Hydroxy, 4,7-dimethoxy and 4-hydroxy, 5-CH3, -CH2OH or -H substitutions on selected indan derivatives produce dopaminergic activity in the cardioaccelerator nerve preparation. 3) 4-Hydroxy-2-di-n-propylaminoindan is stereoselective with the R-isomer being more potent than the S-isomer. One derivative, 4-hydroxy-5-methyl-di-n-propyl-2-aminoindan (RD-211) produced dose-dependent decreases in heart rate and mean arterial pressure. Larger doses also inhibited cardiac responses to stimulation of cardioaccelerator nerve in vivo and in isolated right atria of cats. All of the above responses were significantly inhibited by the dopamine-receptor antagonist sulpiride and not by the alpha 2-adrenoceptor antagonist yohimbine. RD-211 also possesses high affinity for 5-hydroxytryptamine1A receptors as revealed by radioligand binding studies. Results suggest that RD-211 stimulates dopamine DA2-receptors and may also activate 5-hydroxytryptamine1A receptors, but is inactive at alpha 2-adrenoceptors. RD-211 appears not to require metabolic activation even though it has the same chemical moiety as the aminotetralin homolog, which is a dopaminergic prodrug (5-hydroxy-6-methyl-2-di-n-propylaminotetralin).
Details
- Title: Subtitle
- Dopaminergic structure-activity relationships of 2-aminoindans and cardiovascular action and dopaminergic activity of 4-hydroxy, 5-methyl, 2-di-n-propylaminoindan (RD-211)
- Creators
- Shengxing Ma - Department of Pharmacology, College of Medicine, University of Iowa, Iowa City 52242John P LongJan R FlynnPaul A LeonardJoseph G Cannon
- Resource Type
- Journal article
- Publication Details
- The Journal of pharmacology and experimental therapeutics, Vol.256(2), pp.751-756
- Publisher
- United States
- DOI
- 10.1016/S0022-3565(25)22981-0
- PMID
- 1671601
- ISSN
- 0022-3565
- eISSN
- 1521-0103
- Grant note
- HL-38136 / NHLBI NIH HHS
- Language
- English
- Date published
- 02/1991
- Academic Unit
- Anesthesia
- Record Identifier
- 9984006311502771
Metrics
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