Hallucinogen binding to dopamine/neuroleptic receptors

Whitaker, Patricia M.; Seeman, Philip

doi:10.1111/j.2042-7158.1977.tb11381.x

Cited by 31 publications

(4 citation statements)

References 14 publications

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“…The solvent was evaporated under reduced pressure and the residual oil was distilled to give 1.1 g (42%) of 35 as a colorless liquid, bp [115][116][117][118] °C (0.3 mm). The oxalate salt was prepared by adding an anhydrous Et^O solution of the amine to a saturated solution of oxalic acid in Et^O: mp 231-233 °C after recrystallization from MeOH; NMR (free base, CDC13) 1.1 (d, 3 H, CH3), 1.5 (d, 2 H, NH2), 2.25 (s, 3 H, Ar CH3), 2.7 (m, 3 H, CH, CH2), 3.7 (s, 3 H, OCH3), 3.75 (s, 3 H, OCH3), 6.6 (s, 2 H, Ar H); MS (70 eV) m/e (relative intensity) 209 (5), 166 (100). Anal.…”

Section: Methodsmentioning

confidence: 99%

Serotonin receptor affinities of psychoactive phenalkylamine analogs

Glennon¹,

Liebowitz²,

Anderson³

1980

J. Med. Chem.

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Employing a rat fundus model, the serotonin (5-HT) receptor affinities of 45 phenalkylamine analogues were determined. Phenethylamine and phenylisopropylamine possess relatively low receptor affinities; in general, mono-, di-, and trimethoxylation enhance affinity. Of the disubstituted compounds, methoxyl groups at the 2 and 5 positions are optimal for imparting a high affinity. 4-Methylation, 4-ethylation and 4-bromination also enhance receptor affinity, while N,N-dimethylation of the terminal amine decreases affinity. alpha-Methylation of phenethylamines has little effect on affinity when racemates are examined. Introduction of a benzylic keto group can either increase or decrease affinity, depending upon the presence of other aromatic substituents. The most behaviorally active compounds were found to possess the highest 5-HT receptor affinities, while less active compounds were found to possess lower affinities.

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Section: Methodsmentioning

confidence: 99%

Serotonin receptor affinities of psychoactive phenalkylamine analogs

Glennon¹,

Liebowitz²,

Anderson³

1980

J. Med. Chem.

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“…Further, neither in our study nor in that of Trulson, Stark & Jacobs (1977) did DMT produce any turning behaviour in rodents with unilateral 6-OHDA-induced nigrostriatal lesions. It has also been demonstrated that DMT only weakly displaces [3H]-apomorphine or [3H]-dopamine from their receptor binding sites (Burt, Creese & Snyder, 1976;Whitaker & Seeman, 1977) although it is fairly potent in displacing [3H]-haloperidol; nor does DMT stimulate dopamine-sensitive adenylate cyclase in vitro (von Hungen, Roberts & Hill, 1975). It is therefore difficult to attribute the ability of DMT to induce hyperactivity in rodents to a direct agonist action on either cerebral dopamine or 5-HT receptors.…”

Section: Effects Of Adrenoceptor and Dopamine Receptor Antagonists Onmentioning

confidence: 99%

BEHAVIOURAL CHANGES INDUCED BY N,N‐DIMETHYLTRYPTAMINE IN RODENTS

Jenner¹,

Marsden²,

Thanki³

1980

British J Pharmacology

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I N,N-Dimethyltryptamine (DMT) in pargyline pretreated rodents induced a dose-dependent behavioural syndrome consisting of hyperactivity, prostration and hindlimb abduction, mild tremor, Straub tail, retropulsion and jerking. 2 In rats pretreated with pargyline, the behavioural syndrome induced by DMT differed from that induced by L-tryptophan or quipazine, in the lack of forepaw treading and head-weaving and in the presence of only mild tremor. 3 The hyperactivity component of the DMT-induced behavioural syndrome in pargyline-pretreated mice was potentiated by cyproheptadine, methergoline, and mianserin, inhibited by cinanserin, haloperidol, pimozide, methiothepin and propranolol, and not affected by 501C67-sulphate and methysergide. 4 The maximal behavioural changes induced by DMT in rats, other than hyperactivity, were unaffected by pretreatment with cyproheptadine, methysergide, and cinanserin. However, propranolol reduced the intensity of all behavioural effects apart from body jerking, and methergoline decreased the duration of prostration. Phenoxybenzamine and haloperidol, in contrast, enhanced prostration. 5 DMT plus pargyline did not induce circling behaviour in mice with a unilateral 6-hydroxydopamine lesion of the nigro-striatal pathway. 6 The DMT-induced behavioural syndrome appears to consist of two components, (a) hyperactivity and (b) other behavioural changes. They differ in their response to drugs affecting brain monoamines. The hyperactivity component may be expressed via dopamine mechanisms, but the other behavioural changes are not. The two behaviours do not respond consistently to drugs believed to alter brain 5-hydroxytryptamine function.

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“…Although the molecular mechanisms underlying the antiaddictive activity of 1 are not known, the compound displays moderate to high affinity for dopamine and serotonin (5-HT) transporters, κ − and μ opioid receptors, the MK-801 site on the NMDA receptor, ,− σ-2 receptors, ,− nicotine receptors, , and voltage-dependent Na + , K + , and Ca 2+ channels . In the present exploratory study, we compared the in vitro binding profiles of 1 and its principal metabolite noribogaine ( 4 ) with those of the previously described 9 and the isosteric benzothiophenes 17a − d .…”

Section: Resultsmentioning

confidence: 99%

Modified Ibogaine Fragments: Synthesis and Preliminary Pharmacological Characterization of 3-Ethyl-5-phenyl-1,2,3,4,5,6-hexahydroazepino[4,5-b]benzothiophenes

et al. 1998

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Five phenyl-substituted derivatives and analogues of 1,2,3,4,5, 6-hexahydroazepino[4,5-b]indole, 5, a major fragment of ibogaine (1), were synthesized and tested for binding to monoamine transporters, the NMDA receptor-coupled cation channel, and dopamine and opioid receptors. All five derivatives, 9 and 17a-d, displayed 8-10-fold higher affinity at the DA transporter than ibogaine and noribogaine (4). At the serotonin transporter, two compounds (9 and 17a) exhibited higher potency than ibogaine, while the rest had weaker binding affinities than the lead compound. In keeping with their structural similarity to ibogaine, all five compounds displayed weak to poor affinity for dopamine D1 and D2 receptors. However, two compounds, 17a,c, demonstrated moderate binding affinities at dopamine D3 receptors. All five compounds displayed weak to poor affinities for mu and kappa opioid receptors and for the NMDA receptor-coupled cation channel. Despite the qualitative differences, derivatives and analogues of 5may serve as useful substitutes for ibogaine.

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Hallucinogen binding to dopamine/neuroleptic receptors

Cited by 31 publications

References 14 publications

Serotonin receptor affinities of psychoactive phenalkylamine analogs

Serotonin receptor affinities of psychoactive phenalkylamine analogs

BEHAVIOURAL CHANGES INDUCED BY N,N‐DIMETHYLTRYPTAMINE IN RODENTS

Modified Ibogaine Fragments: Synthesis and Preliminary Pharmacological Characterization of 3-Ethyl-5-phenyl-1,2,3,4,5,6-hexahydroazepino[4,5-b]benzothiophenes

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