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Latest revision as of 15:46, 1 November 2024 edit undoJWBE (talk | contribs)Extended confirmed users10,126 edits added Category:Methyl esters using HotCat |
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{{Short description|Chemical compound}} |
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{{Drugbox |
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{{Drugbox |
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| verifiedrevid = 447923549 |
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| verifiedrevid = 449588101 |
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| IUPAC_name = methyl (1R,2S,3S)-3-(4-iodophenyl)-8-methyl -8-azabicyclooctane-2-carboxylate |
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| IUPAC_name = Methyl (1''R'',2''S'',3''S'')-3-(4-iodophenyl)-8-methyl-8-azabicyclooctane-2-carboxylate |
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| image = beta-CIT.png |
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| image = Phenyltropane 11e - RTI-55.svg |
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<!--Clinical data--> |
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<!--Clinical data-->| tradename = |
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| legal_AU = |
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| legal_UK = Class A |
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| legal_CA = |
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| legal_US = Schedule II |
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| legal_UK = Class A |
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| routes_of_administration = <!--Pharmacokinetic data--> |
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| bioavailability = |
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| excretion = <!--Identifiers--> |
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| CAS_number_Ref = {{cascite|correct|??}} |
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| CAS_number = 135416-43-2 |
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| UNII_Ref = {{fdacite|correct|FDA}} |
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| UNII = 4H1Z7121WS |
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| ATC_prefix = |
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| PubChem = 108220 |
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| synonyms = (–)-2β-Carbomethoxy-3β-(4-iodophenyl)tropane; β-CIT; iometopane; iometopane I 123 (USAN); iometopane <sup>123</sup>I (INN); iometopane I 125 (USAN); iometopane <sup>125</sup>I (INN) |
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<!--Pharmacokinetic data--> |
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<!--Chemical data-->| C = 16 |
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| H = 20 |
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| I = 1 |
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| N = 1 |
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| O = 2 |
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| smiles = CN12CC1((C2)C3=CC=C(C=C3)I)C(=O)OC |
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'''RTI(-''4229'')-55''', also called '''RTI-55''' or '''iometopane''', is a ]-based ] used in scientific research and in some medical applications. This drug was first cited in 1991.<ref>{{cite journal | vauthors = Boja JW, Patel A, Carroll FI, Rahman MA, Philip A, Lewin AH, Kopajtic TA, Kuhar MJ | display-authors = 6 | title = RTI-55: a potent ligand for dopamine transporters | journal = European Journal of Pharmacology | volume = 194 | issue = 1 | pages = 133–4 | date = February 1991 | pmid = 2060590 | doi = 10.1016/0014-2999(91)90137-F | url = https://zenodo.org/record/1253870 }}</ref> RTI-55 is a non-selective ] derived from ]. <!--(although it doesn't have to be)--> However, more selective analogs are derived by conversion to "pyrrolidinoamido" ], for instance. Due to the large bulbous nature of the weakly electron withdrawing iodo halogen atom, RTI-55 is the most strongly serotonergic of the simple ''para''-substituted ] based analogs.<ref name=FIC/> In rodents RTI-55 actually caused death at a dosage of 100 mg/kg, whereas RTI-51 and RTI-31 did not.<ref name=FIC>{{cite journal | vauthors = Carroll FI, Runyon SP, Abraham P, Navarro H, Kuhar MJ, Pollard GT, Howard JL | title = Monoamine transporter binding, locomotor activity, and drug discrimination properties of 3-(4-substituted-phenyl)tropane-2-carboxylic acid methyl ester isomers | journal = Journal of Medicinal Chemistry | volume = 47 | issue = 25 | pages = 6401–9 | date = December 2004 | pmid = 15566309 | doi = 10.1021/jm0401311 }}</ref> Another notable observation is the strong propensity of RTI-55 to cause ]s,<ref name=FIC/> although in an earlier study, RTI-51 was actually even stronger than RTI-55 in shifting baseline LMA.<ref>{{cite journal | vauthors = Kimmel HL, Carroll FI, Kuhar MJ | title = Locomotor stimulant effects of novel phenyltropanes in the mouse | journal = Drug and Alcohol Dependence | volume = 65 | issue = 1 | pages = 25–36 | date = December 2001 | pmid = 11714587 | doi = 10.1016/S0376-8716(01)00144-2 }}</ref> This observation serves to highlight the disparities that can arise between studies. |
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<!--Identifiers--> |
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| CAS_number = 133647-95-7 |
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| PubChem = 108220 |
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RTI-55 is one of the most potent phenyltropane stimulants commercially available, which limits its use in humans, as it might have significant abuse potential if used outside a strictly controlled medical setting.<ref>{{cite journal | vauthors = Weed MR, Mackevicius AS, Kebabian J, Woolverton WL | title = Reinforcing and discriminative stimulus effects of beta-CIT in rhesus monkeys | journal = Pharmacology, Biochemistry, and Behavior | volume = 51 | issue = 4 | pages = 953–6 | date = August 1995 | pmid = 7675883 | doi = 10.1016/0091-3057(95)00032-r | s2cid = 53215171 }}</ref> However, it is definitely worthy of mentioning that increasing the size of the halogen atom attached to troparil serves to reduce the number of lever responses in a session when these analogs were compared in a study.<ref>{{cite journal | vauthors = Wee S, Carroll FI, Woolverton WL | title = A reduced rate of in vivo dopamine transporter binding is associated with lower relative reinforcing efficacy of stimulants | journal = Neuropsychopharmacology | volume = 31 | issue = 2 | pages = 351–62 | date = February 2006 | pmid = 15957006 | doi = 10.1038/sj.npp.1300795 | doi-access = free }}</ref> Although RTI-55 wasn't specifically examined in this study the number of lever responses in a given session was of the order cocaine > WIN35428 > RTI-31 > RTI-51. |
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<!--Chemical data--> |
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| C=16 | H=20 | I=1 | N=1 | O=2 |
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| molecular_weight = 385.24 g/mol |
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| smiles = CN12CC1((C2)C3=CC=C(C=C3)I)C(=O)OC |
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'''(–)-2β-Carbomethoxy-3β-(4-iodophenyl)tropane''' ('''β-CIT''', '''RTI-55''', '''iometopane''') is a ]-based psycho] used in scientific research and with some medical application/s.<!--(such as?)--> This drug was first cited in 1991.<ref>{{Cite pmid|2060590}}</ref> RTI-55 is a dirty ] derived from ]. <!--(although it doesn't have to be)--> RTI-55 is one of the most potent phenyltropane stimulants commercially available, which limits its use in humans, as it might have significant abuse potential if used outside of a strictly controlled medical setting.<ref>Weed MR, Mackevicius AS, Kebabian J, Woolverton WL. Reinforcing and discriminative stimulus effects of beta-CIT in rhesus monkeys. ''Pharmacology, Biochemistry and Behaviour''. 1995 Aug;51(4):953-6.</ref> In contrast to ] which is predominantly dopaminergic, increasing the size of the covalently bonded halogen from a chlorine to an iodine markedly increases the affinity for the ], while retaining mostly all of its ] blocking activity. |
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In contrast to ] which is predominantly dopaminergic, increasing the size of the covalently bonded halogen from a chlorine to an iodine markedly increases the affinity for the ], while retaining mostly all of its ] blocking activity. |
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The ] forms of RTI-55, in which the ] atom is ] so that the drug can be used in ], are called iometopane I 123 (]) or iometopane <sup>123</sup>I (]) and iometopane I 125 (USAN) or iometopane <sup>125</sup>I (INN). The ] and ] isotopes are favored because they are very-high-energy ] emitters. |
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If desired, a ] source of ] can be utilized. |
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Compared to the "]" compounds, extremely low ] values are attainable. |
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] and ] in particular because these are very high energy ] emitters. |
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Compared to the "]" compounds, extremely low ] values are attainable. |
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== Uses == |
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== Uses == |
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β-CIT is mainly used in scientific research into the ] reuptake transporter. Various ] forms of β-CIT (with different radioactive ] of ] used depending on the application) are used in both humans and animals to map the distribution of ]s and ]s in the ].<ref>{{Cite pmid|1585258}}</ref><ref>{{Cite pmid|17224717}}</ref> |
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RTI-55 is mainly used in scientific research into the ] reuptake transporter. Various ] forms of RTI-55 (with different radioactive ] of ] used depending on the application) are used in both humans and animals to map the distribution of ]s and ]s in the ].<ref>{{cite journal | vauthors = Shaya EK, Scheffel U, Dannals RF, Ricaurte GA, Carroll FI, Wagner HN, Kuhar MJ, Wong DF | display-authors = 6 | title = In vivo imaging of dopamine reuptake sites in the primate brain using single photon emission computed tomography (SPECT) and iodine-123 labeled RTI-55 | journal = Synapse | volume = 10 | issue = 2 | pages = 169–72 | date = February 1992 | pmid = 1585258 | doi = 10.1002/syn.890100210 | s2cid = 38478862 }}</ref><ref>{{cite journal | vauthors = Shang Y, Gibbs MA, Marek GJ, Stiger T, Burstein AH, Marek K, Seibyl JP, Rogers JF | display-authors = 6 | title = Displacement of serotonin and dopamine transporters by venlafaxine extended release capsule at steady state: a 2beta-carbomethoxy-3beta-(4-iodophenyl)-tropane single photon emission computed tomography imaging study | journal = Journal of Clinical Psychopharmacology | volume = 27 | issue = 1 | pages = 71–5 | date = February 2007 | pmid = 17224717 | doi = 10.1097/JCP.0b013e31802e0017 | s2cid = 25239273 }}</ref> The <sup>123</sup>I derivative is known as iometopane. |
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The main practical application for this drug in medicine is to assess the rate of dopamine neuron degradation in the brains of sufferers of ],<ref>{{Cite pmid|10874697}}</ref><ref>{{Cite pmid|17504864}}</ref> and some other conditions such as ].<ref name="pmid16908744">{{Cite pmid|16908744}}</ref> |
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The main practical application for this drug in medicine is to assess the rate of dopamine neuron degradation in the brains of sufferers of ],<ref>{{cite journal | vauthors = Staffen W, Mair A, Unterrainer J, Trinka E, Bsteh C, Ladurner G | title = beta-CIT binding and SPET compared with clinical diagnosis in parkinsonism | journal = Nuclear Medicine Communications | volume = 21 | issue = 5 | pages = 417–24 | date = May 2000 | pmid = 10874697 | doi = 10.1097/00006231-200005000-00002 }}</ref><ref>{{cite journal | vauthors = Zubal IG, Early M, Yuan O, Jennings D, Marek K, Seibyl JP | title = Optimized, automated striatal uptake analysis applied to SPECT brain scans of Parkinson's disease patients | journal = Journal of Nuclear Medicine | volume = 48 | issue = 6 | pages = 857–64 | date = June 2007 | pmid = 17504864 | doi = 10.2967/jnumed.106.037432 | doi-access = free }}</ref> and some other conditions such as ].<ref name="pmid16908744">{{cite journal | vauthors = Seppi K, Scherfler C, Donnemiller E, Virgolini I, Schocke MF, Goebel G, Mair KJ, Boesch S, Brenneis C, Wenning GK, Poewe W | display-authors = 6 | title = Topography of dopamine transporter availability in progressive supranuclear palsy: a voxelwise beta-CIT SPECT analysis | journal = Archives of Neurology | volume = 63 | issue = 8 | pages = 1154–60 | date = August 2006 | pmid = 16908744 | doi = 10.1001/archneur.63.8.1154 | doi-access = }}</ref> |
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==Chemistry== |
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RTI-55 is made as follows:<ref>{{US Patent|5,128,118}}</ref><ref>{{US Patent|6123917}}</ref><ref>{{cite journal | vauthors = Musachio JL, Keverline KI, Carroll FI, Dannals RF | title = 3 Beta-(p-trimethylsilylphenyl)tropane-2 beta-carboxylic acid methyl ester: a new precursor for the preparation of RTI-55 | journal = Applied Radiation and Isotopes | volume = 47 | issue = 1 | pages = 79–81 | date = January 1996 | pmid = 8589674 | doi = 10.1016/0969-8043(95)00259-6 | doi-access = free }}</ref> |
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==Chemistry== |
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== See also == |
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RTI-55 is made as follows: {{US Patent|5,128,118}} {{US Patent|6123917}}<ref>{{Cite pmid|8589674}}</ref> ] |
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==See also== |
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== References == |
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== References == |
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{{reflist}} |
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{{Reflist}} |
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{{Phenyltropanes}} |
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{{Stimulants}} |
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{{Stimulants}} |
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{{Monoamine reuptake inhibitors}} |
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{{Dopaminergics}} |
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{{Sigma receptor modulators}} |
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{{Phenyltropanes}} |
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