Danuta Marona‐lewicka - The Consciousness Library

Extensive rigid analogue design maps the binding conformation of potent N-benzylphenethylamine 5-HT2A serotonin receptor agonist ligands.

ACS Chemical Neuroscience January 16, 2013 Jose I Juncosa, Martin Hansen, Lisa A Bonner et al.

Based on the structure of the superpotent 5-HT(2A) agonist 2-(4-bromo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine, which consists of a ring-substituted phenethylamine skeleton modified with an N-benzyl group, we designed and synthesized a small library of constrained analogues to identify the optimal arrangement of the pharmacophoric elements of the ligand. Structures consisted...

DOI: 10.1021/cn3000668 Full text

Dopamine D4 receptor involvement in the discriminative stimulus effects in rats of LSD, but not the phenethylamine hallucinogen DOI.

Psychopharmacology April 2009 Danuta Marona‐lewicka, Benjamin R Chemel, David E Nichols

Lysergic acid diethylamide (LSD) differs from other types of hallucinogens in that it possesses direct dopaminergic effects. The exact nature of this component has not been elucidated. The present study sought to characterize the effects of several dopamine D(4) agonists and antagonists on the discriminative stimulus effect of LSD at two pretreatment times and 2,5-dimethoxy-4-iodoamphetamine...

DOI: 10.1007/s00213-008-1238-0 Full text

Further evidence that the delayed temporal dopaminergic effects of LSD are mediated by a mechanism different than the first temporal phase of action.

Pharmacology, biochemistry, and behavior October 2007 Danuta Marona‐lewicka, David E Nichols

Activation of 5-HT(2A) receptors is thought to mediate the hallucinogenic effects of LSD. Nevertheless, in a previous report we provided evidence that a delayed temporal phase of the behavioral pharmacology of LSD is mediated by D(2)-like dopamine receptor stimulation. In this study rats were trained to discriminate LSD with either a 30 min preinjection time (LSD-30, N=12) or a 90 min...

DOI: 10.1016/j.pbb.2007.06.001 Full text

1-Aminomethylbenzocycloalkanes: conformationally restricted hallucinogenic phenethylamine analogues as functionally selective 5-HT2A receptor agonists.

Journal of Medicinal Chemistry September 21, 2006 Thomas H. Mclean, Jason C. Parrish, Michael R Braden et al. 115 citations

A series of conformationally restricted analogues of the hallucinogenic phenethylamine 1 (2,5-dimethoxy-4-bromophenethylamine, 2C-B) was synthesized to test several hypotheses concerning the bioactive conformation of phenethylamine ligands upon binding to the 5-HT(2A) receptor. These benzocycloalkane analogues were assayed for their receptor binding affinity and ability to activate downstream...

DOI: 10.1021/jm060656o Full text LSD Psychopharmacology: neuropharmacology Drug action Brain chemistry +15

C-(4,5,6-Trimethoxyindan-1-yl)methanamine: A Mescaline Analogue Designed Using a Homology Model of the 5-HT2AReceptor

Journal of Medicinal Chemistry June 21, 2006 Thomas H. Mclean, James J. Chambers, Jason C. Parrish et al. 24 citations

A conformationally restricted analogue of mescaline, C-(4,5,6-trimethoxyindan-1-yl)-methanamine, was designed using a 5-HT(2A) receptor homology model. The compound possessed 3-fold higher affinity and potency than and efficacy equal to that of mescaline at the 5-HT(2A) receptor. The new analogue substituted fully for LSD in drug discrimination studies and was 5-fold more potent than mescaline....

DOI: 10.1021/jm060272y Mescaline Potency Stereochemistry Homology modeling +8

Distinct temporal phases in the behavioral pharmacology of LSD: dopamine D2 receptor-mediated effects in the rat and implications for psychosis.

Psychopharmacology July 2005 Danuta Marona‐lewicka, Ronald A Thisted, David E Nichols

The effect of LSD in humans has been described as occurring in two temporal phases. The behavioral effects in rats also occur in two temporal phases: an initial suppression of exploration followed by increased locomotor activity. We decided to investigate this phenomenon from the perspective that the pharmacology might have relevance to the neurochemical mechanisms underlying psychosis....

DOI: 10.1007/s00213-005-2183-9 Full text

Synthesis and Pharmacological Characterization of a Series of Geometrically Constrained 5-HT2A/2C Receptor Ligands

Journal of Medicinal Chemistry July 1, 2003 James J. Chambers, Jason C. Parrish, Niels Jensen et al. 27 citations

In studies of the SAR of phenethylamine-type serotonin 5-HT(2A) receptor agonists, substituted conformationally constrained tetrahydronaphthofurans were designed to investigate the optimal conformation of the 2-aminoethyl moiety. These compounds were tested using in vitro assays for affinity at 5-HT(1A), 5-HT(2A), and 5-HT(2C) receptors. The benzofuran-containing analogues, 6a and 6b, had...

DOI: 10.1021/jm030064v Serotonin Stereochemistry Phenethylamine Intrinsic activity +6

Lysergamides of Isomeric 2,4-Dimethylazetidines Map the Binding Orientation of the Diethylamide Moiety in the Potent Hallucinogenic Agent N,N-Diethyllysergamide (LSD)

Journal of Medicinal Chemistry September 1, 2002 David E. Nichols, Stewart Frescas, Danuta Marona‐lewicka et al. 89 citations

Lysergic acid amides were prepared from (R,R)-(-)-, (S,S)-(+)-, and cis-2,4-dimethyl azetidine. The dimethylazetidine moiety is considered here to be a rigid analogue of diethylamine, and thus, the target compounds are all conformationally constrained analogues of the potent hallucinogenic agent, N,N-diethyllysergamide, LSD-25. Pharmacological evaluation showed that...

DOI: 10.1021/jm020153s Lysergic acid diethylamide Hallucinogen Moiety Stereochemistry +5

Effect of Ring Fluorination on the Pharmacology of Hallucinogenic Tryptamines

Journal of Medicinal Chemistry October 19, 2000 Joseph B. Blair, Deborah Kurrasch‐orbaugh, Danuta Marona‐lewicka et al. 132 citations

A series of fluorinated analogues of the hallucinogenic tryptamines N,N-diethyltryptamine (DET), 4-hydroxy-N,N-dimethyltryptamine (4-OH-DMT, psilocin), and 5-methoxy-DMT was synthesized to investigate possible explanations for the inactivity of 6-fluoro-DET as a hallucinogen and to determine the effects of fluorination on the molecular recognition and activation of these compounds at serotonin...

DOI: 10.1021/jm000339w Serotonin Tryptamines Hallucinogen Partial agonist +5

Further Studies on Oxygenated Tryptamines with LSD-like Activity Incorporating a Chiral Pyrrolidine Moiety into the Side Chain

Journal of Medicinal Chemistry September 16, 1999 Madina R. Gerasimov, Danuta Marona‐lewicka, Deborah Kurrasch‐orbaugh et al. 15 citations

The enantiomers of 3-(N-methylpyrrolidin-2-ylmethyl)-5-methoxyindole, 1, and 3-(N-methylpyrrolidin-2-ylmethyl)-4-hydoxyindole, 3, were prepared using an asymmetric synthesis that employed (+)- or (-)-proline. A new approach was developed that had certain advantages over the synthesis originally reported for the isomers of 1. (+/-)-3-(N-Methylpyrrolidin-3-yl)-4-hydroxyindole, 5, was also...

DOI: 10.1021/jm990325u Enantiomer Stereochemistry Tryptamine Ligand biochemistry +7

Thieno[3,2-b]- and Thieno[2,3-b]pyrrole Bioisosteric Analogues of the Hallucinogen and Serotonin Agonist N,N-Dimethyltryptamine

Journal of Medicinal Chemistry March 1, 1999 Joseph B. Blair, Danuta Marona‐lewicka, Arthi Kanthasamy et al. 63 citations

The synthesis and biological activity of 6-[2-(N, N-dimethylamino)ethyl]-4H-thieno[3,2-b]pyrrole (3a) and 4-[2-(N, N-dimethylamino)ethyl]-6H-thieno[2,3-b]pyrrole (3b), thienopyrroles as potential bioisosteres of N,N-dimethyltryptamine (1a), are reported. Hallucinogen-like activity was evaluated in the two-lever drug discrimination paradigm using LSD- and DOI-trained rats. Neither 3a nor 3b...

DOI: 10.1021/jm980692q Serotonin Tryptamines Hallucinogen Bioisostere +11

A Novel (Benzodifuranyl)aminoalkane with Extremely Potent Activity at the 5-HT2A Receptor

Journal of Medicinal Chemistry December 1, 1998 Matthew Parker, Danuta Marona‐lewicka, Virginia L. Lucaites et al. 69 citations

ADVERTISEMENT RETURN TO ISSUEPREVLetterNEXTA Novel (Benzodifuranyl)aminoalkane with Extremely Potent Activity at the 5-HT2A Receptor 1Matthew A. Parker, Danuta Marona-Lewicka, Virginia L. Lucaites, David L. Nelson, and David E. NicholsView Author Information Department of Medicinal Chemistry and Molecular Pharmacology, School of Pharmacy and Pharmacal Sciences, Purdue University, West...

DOI: 10.1021/jm9803525 Citation Library science Pharmacy World wide web +1

Substituted Naphthofurans as Hallucinogenic Phenethylamine−Ergoline Hybrid Molecules with Unexpected Muscarinic Antagonist Activity

Journal of Medicinal Chemistry May 1, 1998 Aaron Monte, Danuta Marona‐lewicka, Mechelle M. Lewis et al. 20 citations

A series of substituted racemic naphthofurans were synthesized as "hybrid" molecules of the two major prototypical hallucinogenic drug classes, the phenethylamines and the tryptamines/ergolines. Although it was hypothesized that these new agents might possess high affinity for the serotonin 5-HT2A/2C receptor subtypes, unexpected affinity for muscarinic receptors was observed. The compounds...

DOI: 10.1021/jm980076u Serotonin Phenethylamines Muscarinic acetylcholine receptor Stereochemistry +7

Synthesis and Pharmacological Evaluation of Ring-Methylated Derivatives of 3,4-(Methylenedioxy)amphetamine (MDA)

Journal of Medicinal Chemistry February 24, 1998 Matthew Parker, Danuta Marona‐lewicka, Deborah M. Kurrasch et al. 25 citations

The three isomeric ring-methylated derivatives of the well-known hallucinogen and entactogen MDA (1a) were synthesized and evaluated for pharmacological activity as monoamine-releasing agents and as serotonin agonists. The 2-methyl derivative 2a and the 5-methyl derivative 2b were found to be more potent and more selective than the parent compound in inhibiting [3H]-serotonin accumulation in...

DOI: 10.1021/jm9705925 Serotonin Methylenedioxy Pharmacology Hallucinogen +11

ChemInform Abstract: Dihydrobenzofuran Analogues of Hallucinogens. Part 4. Mescaline Derivatives.

ChemInform January 6, 1998 Aaron Monte, Steve R. Waldman, Danuta Marona‐lewicka et al.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

DOI: 10.1002/chin.199801111

Dihydrobenzofuran Analogues of Hallucinogens. 4. Mescaline Derivatives

Journal of Medicinal Chemistry September 1, 1997 Aaron Monte, Steve R. Waldman, Danuta Marona‐lewicka et al. 89 citations

Dihydrobenzofuran and tetrahydrobenzodifuran functionalities were employed as conformationally restricted bioisosteres of the aromatic methoxy groups in the prototypical hallucinogen, mescaline (1). Thus, 4-(2-aminoethyl)-6,7-dimethoxy-2,3-dihydrobenzofuran hydrochloride (8) and 1-(8-methoxy-2,3,5,6-tetrahydrobenzo[1,2-b:5,4-b']difuran-4-yl)-2- aminoethane hydrochloride (9) were prepared and...

DOI: 10.1021/jm970219x Mescaline Serotonin Lysergic acid diethylamide Pharmacology +12

Dihydrobenzofuran Analogues of Hallucinogens. 3. Models of 4-Substituted (2,5-Dimethoxyphenyl)alkylamine Derivatives with Rigidified Methoxy Groups

Journal of Medicinal Chemistry 1996 Aaron Monte, Danuta Marona‐lewicka, Matthew Parker et al. 106 citations

Tetrahydrobenzodifuran functionalities were employed as conformationally restricted bioisosteres of the aromatic methoxy groups in prototypical hallucinogenic phenylalkylamines 1 and 2. Thus, a series of 8-substituted 1-(2,3,6,7-tetrahydrobenzo[1,2-b:4,5-b']difuran-4-yl)-2-aminoal kanes (7a-e) were prepared and evaluated for activity in the two-lever drug discrimination paradigm in rats trained...

DOI: 10.1021/jm960199j Mescaline Serotonin Hallucinogen Ketanserin +11

Stereoselective LSD-like Activity in a Series of d-Lysergic Acid Amides of (R)- and (S)-2-Aminoalkanes

Journal of Medicinal Chemistry March 1, 1995 Aaron Monte, Danuta Marona‐lewicka, Arthi Kanthasamy et al. 25 citations

The 3-pentyl-, (R)- and (S)-2-pentyl-, 2-hexyl-, and 2-heptylamides of d-lysergic acid were synthesized and evaluated in biochemical and behavioral assays for LSD-like activity. In radioligand competition studies, the (R)-lysergamides were consistently more potent than the (S)-amides in displacing [3H]ketanserin from 5-HT2A receptors in rat cortical homogenate and in displacing [3H]-8-OH-DPAT...

DOI: 10.1021/jm00006a015 Lysergic acid diethylamide Stereochemistry Stereoselectivity Carboxamide +3

Papers