Synthesis and radioreceptor binding activity of N-0437, a new, extremely potent and selective D2 dopamine receptor agonist

  title={Synthesis and radioreceptor binding activity of N-0437, a new, extremely potent and selective D2 dopamine receptor agonist},
  author={Alan S. Horn and Pieter G. Tepper and Jan van der Weide and M. Watanabe and Dimitri E. Grigoriadis and Philip Seeman},
  journal={Pharmaceutisch Weekblad},
The synthesis of a new, potent and selective D2 dopamine receptor agonist, N-0437, of the 2-aminotetralin group is described. The results of a radioreceptor binding assay using a homogenate of porcine anterior pituitary as a tissue source for D2 dopamine receptors and3H-spiperone as radioligand demonstrate that this compound is one of the most potent compounds so far evaluated in this test system. 
Radioreceptor binding reveals the potencies of N,N-disubstituted 2-aminotetralins as D2 dopamine agonists
The affinity of a series of N,N-disubstituted 2-aminotetralins for the rat striatal D2 dopamine receptor labelled by [3H]spiperone has been determined and the affinities of the 5-hydroxy-2-aminosine-5′-triphosphate were as high as those of traditional dopamine agonists.
The 2-aminotetralin system as a structural base for new dopamine- and melatonin-receptor agents
The research described in this thesis is divided into two parts; part I deals with the development of a novel 2-aminotetralin as a mixed dopamine Dl/D2-receptor agonist, and part I1 concerns thedevelopment of 2-amidOTetralins as nonindolic melatonin-recept agents.
Ligands for the dopamine D 2-like receptors
This study synthesized a series of substituted N-(1-benzyl-piperidin-4-yl)benzamides with varying degrees of DA D4 selectivity, and tested four of these benzamides for their ability to inhibit Damphetamine-induced hyperactivity in the rat.
The metabolic fate of the dopamine agonist 2-(N-propyl-N-2-thienylethylamino)-5-hydroxytetralin in rats after intravenous and oral administration. II. Isolation and identification of metabolites.
In vivo metabolic pathways of 2-(N-propyl-N-2-thienylethylamino)-5-hydroxytetralin in rats have been established, using in vitro metabolism as a complementary technique, and glucuronide and sulphate conjugates were identified.
Determination of the dopamine D2 agonist N-0923 and its major metabolites in perfused rat livers by HPLC-UV-atmospheric pressure ionization mass spectrometry.
The metabolism of the dopamine D2 agonist N-0923 was investigated by an in vitro isolated liver perfusion. Determining the metabolic profile and identity of the different metabolites was achieved by
Optical Control of Dopamine Receptors Using a Photoswitchable Tethered Inverse Agonist.
The results indicate that DARs can be chemically engineered for selective remote control by light and provide a template for precision control of Family A GPCRs.
Dopaminergic regulation of striatal cholinergic interneurons: an in vivo microdialysis study
The results of this study reemphasize the importance of the calcium concentration in determining the effects of drugs on central neurotransmitter release, and confirm a role of dopamine in the regulation of striatal cholinergic interneurons.
The Gαi protein subclass selectivity to the dopamine D2 receptor is also decided by their location at the cell membrane
This study showed that even closely related subunits of Gαi differ in their membrane-trafficking properties that impact on their signaling, and should therefore be taken into account as one of the selectivity determinants of G protein coupling.
The anorectic effect of SK&F 38393, a selective dopamine D1 receptor agonist: a microstructural analysis of feeding and related behaviour
An observational study was undertaken to provide a microstructural analysis of the effects of the selective dopamine D1 receptor agonist, SK&F 38393, on feeding and associated behaviours in the rat, suggesting that SK&f 38393 did not materially affect the form and sequence of behavioural responses in the test, although some changes occurred.


The role of D-1 and D-2 receptors
Motor and endocrine effects in parkinsonian subjects seem to depend on drug interaction with D-2, but not D-1, receptors, which may have important implications for the design of anti-parkinsonian and antipsychotic agents.
A comparison of the potencies of various dopamine receptor agonists in models for pre- and postsynaptic receptor activity
It may be concluded that N,N-dipropyl-2-amino-7-hydroxytetralin shows the largest difference in activity in the biochemical and the behavioural models, suggesting a selective presynaptic activity.
N-Alkylated 2-aminotetralins: central dopamine-receptor stimulating activity.
From the biochemical data it is concluded that an n-propyl group on the nitrogen is optimal for activity, and it is suggested that a possible requirement for a potent agonist is that one of it N substituents must fit into a receptor cavity which, because of its size, can maximally accommodate an n -propyl but also smaller groups like ethyl or methyl.
The Dopamine/Neuroleptic Receptor
  • D. Grigoriadis, P. Seeman
  • Biology, Psychology
    Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques
  • 1984
The neuroleptic/dopamine receptor, with its picomolar affinity for potent neuroleptics, is the functional dopamine receptor of the brain, and it inhibits or interferes with dopamine-stimulated adenylate cyclase.
Further characterization of structural requirements for agonists at the striatal dopamine D2 receptor and a comparison with those at the striatal dopamine D1 receptor. Studies with a series of monohydroxyaminotetralins on acetylcholine release from rat striatum.
A series of phenolic hydroxy-2-aminotetralins with either a primary or a tertiary amino group was investigated on electrically evoked acetylcholine release from striatal slices of reserpinized rats, suggesting two similar major binding sites for the DA receptor subtypes, but differences with respect to additional binding sites.
Neurochemical and behavioural profiles of five dopamine analogues
In going from the simple dopamine-like structure to the aminotetralin compound there has been an increase in dopamine agonist-like activity.
Functional States of Dopamine Receptors
Dopamine receptors can exist in either a high-affinity state or in a low-Affinity state for dopamine agonists for guanine nucleotides.