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Chromanamines: A New Group of Psychedelics?

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Lilienthal:
Sorry, the Glennon article was about amino-analogs of chromanes (tetrahydrochinolines).

[edited]
Hit me, I was wrong again. That paper was about tetrahydroisochinolines not related to your chromanes.
[/edited]

But here are some chemistry references directly from Beilstein:

Bioorg. Med. Chem. 7: 335 (1999): 6-methoxy-3-amino-chromane
J. Org. Chem. 63: 5362 (1998): (R)/(S)/(R/S)-3-aminochromane
Pharm. Pharmacol. Commun. 1: 47 (1998): 6,7-ethylendioxy-3-amino-chromane
Eur. J. Med. Chem.Chim.Ther. 26: 497 (1991):5-methoxy-3-amino-chromane, 6,7-dimethoxy-3-amino-chromane, 7-methoxy-3-amino-chromane

Lion:
Interesting stuff to theorize about... very structurally similar to 2-aminotetralin. 

Be aware... 2-aminotetralin is a very nasty nasty compound.  That goes for 2-aminoindane also...

It's quite aasy to be fooled by the animal data and binding studies.  Extrapolating data to humans
is very tricky bizness, and many times it's simply not the same.  Contrary to what the Nichols and Glennon studies point towards, the tetralin compound is nothing at all like amphetamine.  It's ten billion universes in the opposite direction. 

Don't go there girlfriend!

Best Regards,

The Lion

Youjutsu:
How do you connect to Beilstein?  What server do you use?  I've used the program before and I couldn't figure out how to use it, but I don't think I messed with it for more than a few minutes.

I've found some other interesting references:

TITLE:  5-HT1A receptor agonists prevent in rats the yawning and penile erections induced by direct dopamine agonists.
AUTHORS:  Simon P; Guardiola B; Bizot-Espiard J; Schiavi P; Costentin J
AUTHOR AFFILIATION:  Unite de Neuropsychopharmacologie, U.R.A. 1170 du C.N.R.S., Faculte de Medecine et Pharmacie de Rouen, Saint Etienne du Rouvray, France.
SOURCE:  Psychopharmacology (Berl) 1992;108(1-2):47-50
CITATION IDS:  PMID: 1357709 UI: 93029100
ABSTRACT:  The new compound (+) S-20499, an amino chromane derivative (8[-4[N-(5-methoxychromane-3yl)N-propyl]aminobutyl] azaspiro[4-5] decane-7,9 dione), is a high affinity full 5-HT1A agonist. We have investigated its effects on dopaminergic transmission. (+) S-20499 displayed a 10(-8) M affinity for D2 dopamine (DA) receptors, 100 fold lower than for 5-HT1A receptors. The hypothermic effect of the drug was reversed by haloperidol in mice, suggesting that it behaves as a direct dopamine agonist. However, increasing doses of (+) S-20499 induced neither yawning nor penile erections, which constitute characteristic responses of direct DA agonists administered at low doses. In addition, (+) S-20499 prevented the apomorphine (100 micrograms/kg SC) induced yawning and penile erections. This inhibition appears to result from the stimulation of 5-HT1A receptors since it is an effect shared by both buspirone (from 5 mg/kg) and 8-OH-DPAT (from 0.10 mg/kg). In addition, when rats are treated with the 5-HT1A receptor antagonist tertatolol (2-5 mg/kg; SC), increasing doses of (+) S-20499 elicit the expected yawns and penile erections. It is concluded that the 5-HT1A agonist property opposes to that of D2 dopamine receptor stimulation with regard to yawning and penile erections.


TITLE:  Enhancement of cortical and hippocampal cholinergic neurotransmission through 5-HT1A receptor-mediated pathways by BAY x 3702 in freely moving rats.
AUTHORS:  Koyama T; Nakajima Y; Fujii T; Kawashima K
AUTHOR AFFILIATION:  Department of Pharmacology, Kyoritsu College of Pharmacy, Tokyo, Japan.
SOURCE:  Neurosci Lett 1999 Apr 9;265(1):33-6
CITATION IDS:  PMID: 10327199 UI: 99257131
ABSTRACT:  Involvement of serotonin (5-HT) in the regulation of cholinergic neuronal activity by modulation of acetylcholine (ACh) release has been reported for various regions of the brain. Cortical and hippocampal cholinergic neurotransmission is of particular importance in the mechanisms of attention as well as learning and memory. In the present study, we investigated the effect of R-(-)-2-[4-[(chroman-2-yl-methyl)-amino-butyl]-1,1-dioxo-benzo[d]++ +isothiazolone hydrochloride (BAY x 3702), a novel, high-affinity 5-HT1A receptor agonist, on ACh release in the cerebral cortex and hippocampus of freely moving rats using an in vivo microdialysis technique. Acetylcholine efflux from the cortex and hippocampus was measured every 30 m using a sensitive and specific radioimmunoassay and was stable for at least 5 h. The ACh efflux from the cortex and hippocampus was increased significantly by BAY x 3702 (0.3 mg/kg, i.p.) compared with saline administration. WAY-100635 (0.6 mg/kg, s.c.), a selective 5-HT1A receptor antagonist, eliminated the augmentation of ACh efflux induced by BAY x 3702 in both brain regions. These results demonstrate that stimulation by BAY x 3702 enhanced ACh release in both the cortex and hippocampus through 5-HT1A receptor-mediated pathways.


TITLE:  Discriminative stimulus properties of the 5-HT1A receptor agonist BAY x 3702 in the rat.
AUTHORS:  De Vry J; Jentzsch KR
AUTHOR AFFILIATION:  CNS Research, Bayer, Cologne, Germany. jean.vry.jv@bayer-ag.de
SOURCE:  Eur J Pharmacol 1998 Sep 11;357(1):1-8
CITATION IDS:  PMID: 9788767 UI: 99002816
ABSTRACT:  The aminomethylchroman derivative BAY x 3702 (R-(-)-2-4-[(chroman-2-ylmethyl)-amino]-butyl-1,1-dioxo-benzo[d] isothiazolone HCl) has recently been characterized as a relatively selective, high affinity 5-HT1A receptor agonist with neuroprotective, anxiolytic- and antidepressant-like effects in animal models. It was the aim of the present study to further confirm its receptor binding profile in an in vivo assay. Rats were trained to discriminate BAY x 3702 (0.1 mg/kg, i.p.) from vehicle in a standard two-lever fixed ratio 10 food-reinforced procedure. All rats learned the discrimination, the median number of sessions to reach criterion being 38 (range: 22-58 sessions). Generalization tests with BAY x 3702 showed dose-dependent and complete generalization after different routes of administration; the ED50 values being: 0.030, 0.007 and 0.36 mg/kg, after i.p., i.v. and p.o. administration, respectively. Assessment of the duration of action after administration of 0.1 mg/kg BAY x 3702, i.p., resulted in a T1/2 of 65 min. Dose-dependent and complete generalization was also obtained with the 5-HT1A receptor agonists 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)-tetralin, ED50 in mg/kg, i.p.: 0.086), flesinoxan (0.30), SR 57746A ((4-(3-trifluoromethylphenyl)-N-(2-(naphth-2-yl)ethyl)-1,2,3,6-tet rahydropyridine HCl, 1.0), the (+)-enantiomer of BAY x 3702 (1.3) and ipsapirone (1.8); the ED50 values being closely correlated with their respective affinities for the 5-HT1A receptor. Pretreatment with the selective 5-HT1A receptor antagonist WAY-100635 ((N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N(2-pyridinyl) cyclohexane carboxamide trihydrochloride) dose-dependently and completely blocked the discriminative effects of 0.1 mg/kg BAY x 3702 (ID50: 0.013 mg/kg, i.p.). WAY-100635, prazosin, idazoxan, raclopride, paroxetine, (-)-BAY k 8644 (methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoro-methyl-phenyl)-p yridine-5-carboxylate), ethanol, and the putative neuroprotectants MK-801 ((+)-5-methyl-10,11-dihydroxy-5H-dibenzo(a,d)cyclohepten-5,10-imin e), CNS 1102 (N-(1-naphthyl)-N'-(3-ethylphenyl)-N'-methyl-guanidine), CGS 19755 (cis-4-(phosphonomethyl) piperidine-2-carboxylic acid) and nimodipine did not induce more than 20% generalization. It is concluded that the BAY x 3702 cue is mediated by its agonistic activity at 5-HT1A receptors.


TITLE:  Characterization of the aminomethylchroman derivative BAY x 3702 as a highly potent 5-hydroxytryptamine1A receptor agonist.
AUTHORS:  De Vry J; Schohe-Loop R; Heine HG; Greuel JM; Mauler F; Schmidt B; Sommermeyer H; Glaser T
AUTHOR AFFILIATION:  CNS Research, Troponwerke GmbH & Co. KG, Cologne, FRG.
SOURCE:  J Pharmacol Exp Ther 1998 Mar;284(3):1082-94
CITATION IDS:  PMID: 9495870 UI: 98173751
ABSTRACT:  The aminomethylchroman derivative BAY x 3702 (R-(-)-2-[4-[(chroman-2-ylmethyl)-amino]-butyl]-1,1-dioxo-benzo[d] isothiazolone hydrochloride) is a new high affinity 5-hydroxytryptamine (5-HT)1A receptor ligand [calf hippocampus: Ki: 0.19 nM; reference compounds 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) and ipsapirone: 0.98 and 2.56, respectively; rat cortex: 0.24 nM; rat hippocampus: 0.58 nM; human cortex and recombinant 5-HT1A receptors: 0.25 and 0.4 nM, respectively]. BAY x 3702 bound also with relatively high to moderate affinity to the following receptors: alpha-1 and alpha-2 adrenergic (Ki: 6 and 7 nM, respectively); 5-HT7- and 5-HT1D (7 and 36 nM); dopamine D2- and D4 (48 and 91 nM); sigma sites (176 nM) and 5-HT2C (310 nM); others: > 10 microM, as obtained in more than 50 different binding assays. In the forskolin-stimulated adenylate cyclase assay in rat hippocampal tissue, a model of postsynaptic 5-HT1A receptor function, BAY x 3702 was a potent 5-HT1A receptor full agonist (IC50: 1.9 nM; 8-OH-DPAT: 25.3 nM, full agonist; ipsapirone: partial agonist) and its effects could be completely blocked by the 5-HT1A receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohe xan e carboxamide trihydrochloride (WAY-100635). At those receptors where BAY x 3702 bound with lower affinity, the compound appeared to be either an agonist (5-HT1D receptors) or an antagonist (alpha-1, alpha-2 and D2 receptors). In a rat brain slice preparation containing the dorsal raphe nucleus (DRN), a model of somatodendritic 5-HT1A receptor function, BAY x 3702 inhibited potently (1 nM) neuronal firing. Also in vivo, BAY x 3702 (0.5 microgram/kg, i.v.) was found to suppress 5-HT neuronal firing in the DRN of anesthetized rats. In both electrophysiological assays BAY x 3702 was more potent than 8-OH-DPAT and ipsapirone; the potency difference being about 1 and 2 orders of magnitude, respectively. In rats trained to discriminate 8-OH-DPAT (0.1 mg/kg, i.p.) in a drug discrimination procedure, complete generalization was obtained with BAY x 3702 (ED50: 0.022 mg/kg, i.p. and 0.38 mg/kg, p.o.; 8-OH-DPAT: 0.028 mg/kg, i.p. and ipsapirone: 0.44 mg/kg, i.p.). In the rat hypothermia model BAY x 3702 induced a WAY-100635-reversible effect and the compound had a higher potency and intrinsic activity than 8-OH-DPAT and ipsapirone (ED50: 0.25 mg/kg, i.p. and 5.4 mg/kg, p.o., respectively; 8-OH-DPAT: 1.1 mg/kg, i.p. and ipsapirone: 6.2 mg/kg, i.p.). BAY x 3702 induced a stimulation of plasma ACTH levels in the rat; the effect being again more pronounced than that of ipsapirone (ED50: 7.5 and 25.3 mg/kg, p.o., respectively). It is concluded that BAY x 3702 is a relatively selective 5-HT1A receptor agonist with high potency and intrinsic activity.


TITLE:  Cycloaddition of dichloroketene to N,N-disubstituted 3-aminomethylene-5-hydroxy-2,2-dimethyl-7-pentyl-4-chromanone: synthesis of 2H,5H-pyrano[3,2-c][1]benzopyran derivatives.
AUTHORS:  Cafaggi S; Romussi G; Ciarallo G; Bignardi G
SOURCE:  Farmaco [Sci] 1983 Oct;38(10):775-83
CITATION IDS:  PMID: 6139296 UI: 84058312
ABSTRACT:  The synthesis of N,N-disubstituted 3-aminomethylene-5-hydroxy-2,2-dimethyl-7-pentyl-4-chromanones (III) and their reaction with dichloroketene are described. The resulting cycloadducts (IV) gave, by dehydrochlorination, the N,N-disubstituted 4-amino-3-chloro-10-hydroxy-5,5-dimethyl-8-pentyl-2H,5H-pyrano[3,2-c] [1]benzopyran-2-ones (V), which are structurally related to tetrahydrocannabinols. Only the compound (V a) displayed a very weak stimulant activity on the CNS.


TITLE:  Stereoselective synthesis of cis- and trans-3-amino-4-chromanols.
AUTHORS:  Sugihara H; Sanno Y
SOURCE:  Chem Pharm Bull (Tokyo) 1977 May;25(5):859-66
CITATION IDS:  PMID: 45506 UI: 87187845


Well, that's just about all I could find that was even remotely interesting.

Laters,

Youjutsu, Nemesis, PsiliPharm, etc...

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