Stereoselective effects of the potentially neuroleptic rigid spiro amines

ABSTRACT WE HAVE reported the synthesis and pharmacological effects of a novel series of tetracyclic spiro compounds structurally related to the tricyclic antidepressants1. In contrast to

the common tricyclic antidepressants, the terminal amino group of the spiro compounds has restricted mobility. As expected, some of these compounds have antidepressant properties in model

systems, for example they are potent blockers of the neuronal uptake of noradrenaline in the central nervous system. But the compounds containing a chlorine atom in the tricyclic moiety have

a neuroleptic profile in animal tests. 3-Chloro-10,11-dihydro-N,N-dimethylspiro-[5H-dibenzo [_a,d_]cycloheptene-5,1′-cyclohex-2′-ene]-4′-amine, structure (I), is particularly interesting in

this respect. The cyclohexene ring in this structure is located perpendicularly to the tricyclic ring system and as a consequence the amino group can occupy a position either _cis_ or

_trans_ to the chlorine-containing part of the tricyclic ring system. Furthermore, the _cis_ and _trans_ isomers can be resolved into enantiomers as the molecule contains two chiral centres

(marked with asterisks in structure (I)). Several studies have yielded results to favour the view that neuroleptic drugs act as dopamine (DA) antagonists in the brain2,3 and that the DA

receptor blockade is rather well correlated with their antipsychotic efficiency4–6. The neuroleptics seem to block chiefly postsynaptic DA receptors, particularly in striatal7 and

mesolimbic8 DA areas of the brain. The rigid nature of the isomeric tetracyclic spiro amines of structure (I), and the possibility of stereospecific pharmacological effects make these

compounds interesting tools for an investigation of the structural requirements for DA receptor blockade and for studies on DA receptor topology. Access through your institution Buy or

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(2-AMINOPROPYL)BENZO[Β]THIOPHENES (APBTS) ARE NOVEL MONOAMINE TRANSPORTER LIGANDS THAT LACK STIMULANT EFFECTS BUT DISPLAY PSYCHEDELIC-LIKE ACTIVITY IN MICE Article 08 November 2021

STRUCTURE-BASED DESIGN OF A NOVEL THIRD-GENERATION ANTIPSYCHOTIC DRUG LEAD WITH POTENTIAL ANTIDEPRESSANT PROPERTIES Article 09 December 2021 STRUCTURE OF THE DOPAMINE D2 RECEPTOR IN COMPLEX

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Pharmac._, 10, 759–766 (1974). CAS  Google Scholar  Download references AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Organic Chemistry, Research and Development Laboratories,

Astra Läkemedel AB, S-151 85, Södertälje, Sweden BERNT CARNMALM, LARS JOHANSSON, STEN RÄMSBY & NILS E. STJERNSTRÖM * Department of Pharmacology, Research and Development Laboratories,

Astra Läkemedel AB, S-151 85, Södertälje, Sweden SVANTE B. ROSS & SVEN-OVE OGREN Authors * BERNT CARNMALM View author publications You can also search for this author inPubMed Google

Scholar * LARS JOHANSSON View author publications You can also search for this author inPubMed Google Scholar * STEN RÄMSBY View author publications You can also search for this author

inPubMed Google Scholar * NILS E. STJERNSTRÖM View author publications You can also search for this author inPubMed Google Scholar * SVANTE B. ROSS View author publications You can also

search for this author inPubMed Google Scholar * SVEN-OVE OGREN View author publications You can also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and

permissions ABOUT THIS ARTICLE CITE THIS ARTICLE CARNMALM, B., JOHANSSON, L., RÄMSBY, S. _et al._ Stereoselective effects of the potentially neuroleptic rigid spiro amines. _Nature_ 263,

519–520 (1976). https://doi.org/10.1038/263519a0 Download citation * Received: 11 June 1976 * Accepted: 24 August 1976 * Issue Date: 07 October 1976 * DOI: https://doi.org/10.1038/263519a0

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