RTI-55

RTI-55
Clinical data
Other names	(–)-2β-Carbomethoxy-3β-(4-iodophenyl)tropane; β-CIT; iometopane; iometopane I 123 (USAN); iometopane 123I (INN); iometopane I 125 (USAN); iometopane 125I (INN)
Legal status
Legal status	UK: Class A; US: Schedule II;
Identifiers
	IUPAC name Methyl (1R,2S,3S)-3-(4-iodophenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate;
CAS Number	135416-43-2 ;
PubChem CID	108220;
UNII	4H1Z7121WS;
CompTox Dashboard (EPA)	DTXSID801126429 ;
Chemical and physical data
Formula	C16H20INO2
Molar mass	385.245 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CN1[C@H]2CC[C@@H]1[C@H]([C@H](C2)C3=CC=C(C=C3)I)C(=O)OC;
	(verify)

RTI(-4229)-55, also called RTI-55 or iometopane, is a phenyltropane-based psychostimulant used in scientific research and in some medical applications. This drug was first cited in 1991.^[1] RTI-55 is a non-selective dopamine reuptake inhibitor derived from methylecgonidine. However, more selective analogs are derived by conversion to "pyrrolidinoamido" RTI-229, 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 troparil based analogs.^[2] In rodents RTI-55 actually caused death at a dosage of 100 mg/kg, whereas RTI-51 and RTI-31 did not.^[2] Another notable observation is the strong propensity of RTI-55 to cause locomotor activity enhancements,^[2] although in an earlier study, RTI-51 was actually even stronger than RTI-55 in shifting baseline LMA.^[3] This observation serves to highlight the disparities that can arise between studies.

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.^[4] 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.^[5] 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.

In contrast to RTI-31 which is predominantly dopaminergic, increasing the size of the covalently bonded halogen from a chlorine to an iodine markedly increases the affinity for the SERT, while retaining mostly all of its DAT blocking activity.

The radiopharmaceutical forms of RTI-55, in which the iodine atom is radioiodine so that the drug can be used in single-photon emission computed tomography, are called iometopane I 123 (USAN) or iometopane ¹²³I (INN) and iometopane I 125 (USAN) or iometopane ¹²⁵I (INN). The ¹²³I and ¹²⁵I isotopes are favored because they are very-high-energy γ-ray emitters.

Compared to the "WIN" compounds, extremely low K_i values are attainable.

^ Boja JW, Patel A, Carroll FI, Rahman MA, Philip A, Lewin AH, et al. (February 1991). "[125I]RTI-55: a potent ligand for dopamine transporters". European Journal of Pharmacology. 194 (1): 133–4. doi:10.1016/0014-2999(91)90137-F. PMID 2060590.
^ ^a ^b ^c Carroll FI, Runyon SP, Abraham P, Navarro H, Kuhar MJ, Pollard GT, Howard JL (December 2004). "Monoamine transporter binding, locomotor activity, and drug discrimination properties of 3-(4-substituted-phenyl)tropane-2-carboxylic acid methyl ester isomers". Journal of Medicinal Chemistry. 47 (25): 6401–9. doi:10.1021/jm0401311. PMID 15566309.
^ Kimmel HL, Carroll FI, Kuhar MJ (December 2001). "Locomotor stimulant effects of novel phenyltropanes in the mouse". Drug and Alcohol Dependence. 65 (1): 25–36. doi:10.1016/S0376-8716(01)00144-2. PMID 11714587.
^ Weed MR, Mackevicius AS, Kebabian J, Woolverton WL (August 1995). "Reinforcing and discriminative stimulus effects of beta-CIT in rhesus monkeys". Pharmacology, Biochemistry, and Behavior. 51 (4): 953–6. doi:10.1016/0091-3057(95)00032-r. PMID 7675883. S2CID 53215171.
^ Wee S, Carroll FI, Woolverton WL (February 2006). "A reduced rate of in vivo dopamine transporter binding is associated with lower relative reinforcing efficacy of stimulants". Neuropsychopharmacology. 31 (2): 351–62. doi:10.1038/sj.npp.1300795. PMID 15957006.

[1] Boja JW, Patel A, Carroll FI, Rahman MA, Philip A, Lewin AH, et al. (February 1991). "[125I]RTI-55: a potent ligand for dopamine transporters". European Journal of Pharmacology. 194 (1): 133–4. doi:10.1016/0014-2999(91)90137-F. PMID 2060590.

[FIC-2] Carroll FI, Runyon SP, Abraham P, Navarro H, Kuhar MJ, Pollard GT, Howard JL (December 2004). "Monoamine transporter binding, locomotor activity, and drug discrimination properties of 3-(4-substituted-phenyl)tropane-2-carboxylic acid methyl ester isomers". Journal of Medicinal Chemistry. 47 (25): 6401–9. doi:10.1021/jm0401311. PMID 15566309.

[3] Kimmel HL, Carroll FI, Kuhar MJ (December 2001). "Locomotor stimulant effects of novel phenyltropanes in the mouse". Drug and Alcohol Dependence. 65 (1): 25–36. doi:10.1016/S0376-8716(01)00144-2. PMID 11714587.

[4] Weed MR, Mackevicius AS, Kebabian J, Woolverton WL (August 1995). "Reinforcing and discriminative stimulus effects of beta-CIT in rhesus monkeys". Pharmacology, Biochemistry, and Behavior. 51 (4): 953–6. doi:10.1016/0091-3057(95)00032-r. PMID 7675883. S2CID 53215171.

[5] Wee S, Carroll FI, Woolverton WL (February 2006). "A reduced rate of in vivo dopamine transporter binding is associated with lower relative reinforcing efficacy of stimulants". Neuropsychopharmacology. 31 (2): 351–62. doi:10.1038/sj.npp.1300795. PMID 15957006.

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