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.
Compared to the "
WIN" compounds, extremely low
Ki values are attainable.
Uses
RTI-55 is mainly used in scientific research into the
dopamine reuptake transporter. Various
radiolabelled forms of RTI-55 (with different radioactive
isotopes of
iodine used depending on the application) are used in both humans and animals to map the distribution of
dopamine transporters and
serotonin transporters in the
brain.[6][7] The 123I derivative is known as iometopane.
The main practical application for this drug in medicine is to assess the rate of dopamine neuron degradation in the brains of sufferers of
Parkinson's disease,[8][9] and some other conditions such as
progressive supranuclear palsy.[10]
^Shaya EK, Scheffel U, Dannals RF, Ricaurte GA, Carroll FI, Wagner HN, et al. (February 1992). "In vivo imaging of dopamine reuptake sites in the primate brain using single photon emission computed tomography (SPECT) and iodine-123 labeled RTI-55". Synapse. 10 (2): 169–72.
doi:
10.1002/syn.890100210.
PMID1585258.
S2CID38478862.
^Shang Y, Gibbs MA, Marek GJ, Stiger T, Burstein AH, Marek K, et al. (February 2007). "Displacement of serotonin and dopamine transporters by venlafaxine extended release capsule at steady state: a [123I]2beta-carbomethoxy-3beta-(4-iodophenyl)-tropane single photon emission computed tomography imaging study". Journal of Clinical Psychopharmacology. 27 (1): 71–5.
doi:
10.1097/JCP.0b013e31802e0017.
PMID17224717.
S2CID25239273.
^Staffen W, Mair A, Unterrainer J, Trinka E, Bsteh C, Ladurner G (May 2000). "[123I] beta-CIT binding and SPET compared with clinical diagnosis in parkinsonism". Nuclear Medicine Communications. 21 (5): 417–24.
doi:
10.1097/00006231-200005000-00002.
PMID10874697.