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An alternative approach to developing dopamine‐receptor agonists with central presynaptic actions following oral administration: A comparison between apomorphine, bromocriptine, and the novel compound RDS‐127 (2‐di‐n‐propylamino‐4,7‐dimethoxyindane)
Author(s) -
Arnerić Stephen P.,
Long John P.
Publication year - 1983
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430030304
Subject(s) - bromocriptine , apomorphine , agonist , pharmacology , sulpiride , dopamine receptor , autoreceptor , locomotor activity , dopamine agonist , chemistry , dopamine , oral administration , endocrinology , medicine , receptor , dopaminergic , prolactin , hormone
RDS‐127 (2‐di‐n‐propylamino‐4,7‐dimethoxyindane) is a novel dopamine (DA) receptor agonist with potent central actions. RDS‐127, apomorphine (APO), and bromocriptine (BRM) were compared for their ability to inhibit locomotor activity in rats following oral administration. APO, BRM, and RDS‐127 produced time‐ and dose‐dependent decreases in locomotor activity. While APO and BRM were equipotent in inhibiting locomotor activity, RDS‐127 was 13.5 times more potent than either APO or BRM. A single oral dose of 32.0 μmol/kg of RDS‐127 decreased locomotor activity greater than 50% for a period of 2 hr. The inhibitory effects of RDS‐127 on locomotor activity were blocked by prior administration of sulpiride, suggesting the effects are mediated by DA receptors. While oral administration of APO or RDS‐127 generally decreased locomotor activity, similar doses given subcutaneously increased locomotor activity. These data suggest that the route of administration can profoundly affect the biological actions of DA receptor agonists and the accompanying conclusions concerning the selectivity with which they interact with different receptor subtypes. The therapeutic application and design of orally effective DA autoreceptor agonists are discussed.