RTI(-''4229'')-55, also called RTI-55 or iometopane, is a
phenyltropane
Phenyltropanes (PTs) were originally developed to reduce cocaine addiction and dependency. In general these compounds act as inhibitors of the plasmalemmal monoamine reuptake transporters. Although RTI holds a strong position in this field, ...
-based
psychostimulant used in scientific research and in some medical applications. This drug was first cited in 1991. RTI-55 is a non-selective
dopamine reuptake inhibitor
A dopamine reuptake inhibitor (DRI) is a class of drug which acts as a reuptake inhibitor of the monoamine neurotransmitter dopamine by blocking the action of the dopamine transporter (DAT). Reuptake inhibition is achieved when extracellular dopa ...
derived from
methylecgonidine
Methylecgonidine (anhydromethylecgonine; anhydroecgonine methyl ester; AEME) is a chemical intermediate derived from ecgonine or cocaine.
Methylecgonidine is a pyrolysis product formed when crack cocaine is smoked, making this substance a useful ...
. However, more selective analogs are derived by conversion to "pyrrolidinoamido"
RTI-229
RTI-229, also known as (–)-3β-(4-iodophenyl)tropane-2β-pyrrolidine carboxamide and RTI-''4229''-229, is a potent and long-lasting stimulant drug which was developed in the 1990s as part of a large group of related analogues from the phenylt ...
, 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
Troparil (also known as (–)-2β-Carbomethoxy-3β-phenyltropane, WIN 35,065-2, or β-CPT) is a stimulant drug used in scientific research. Troparil is a phenyltropane-based dopamine reuptake inhibitor (DRI) that is derived from methylecgonidine ...
based analogs.
[ In rodents RTI-55 actually caused death at a dosage of 100 mg/kg, whereas RTI-51 and RTI-31 did not.] Another notable observation is the strong propensity of RTI-55 to cause locomotor activity enhancements,[ although in an earlier study, RTI-51 was actually even stronger than RTI-55 in shifting baseline LMA. 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. 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. 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
(–)-2β-Carbomethoxy-3β-(4'-chlorophenyl)tropane (RTI-''4229''-31) is a synthetic analog of cocaine that acts as a stimulant. Semi-synthesis of this compound is dependent upon the availability of cocaine starting material. According to the ar ...
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
Radiopharmaceuticals, or medicinal radiocompounds, are a group of pharmaceutical drugs containing radioactive isotopes. Radiopharmaceuticals can be used as diagnostic and therapeutic agents. Radiopharmaceuticals emit radiation themselves, which ...
forms of RTI-55, in which the iodine
Iodine is a chemical element with the symbol I and atomic number 53. The heaviest of the stable halogens, it exists as a semi-lustrous, non-metallic solid at standard conditions that melts to form a deep violet liquid at , and boils to a vi ...
atom is radioiodine
There are 37 known isotopes of iodine (53I) from 108I to 144I; all undergo radioactive decay except 127I, which is stable. Iodine is thus a monoisotopic element.
Its longest-lived radioactive isotope, 129I, has a half-life of 15.7 million year ...
so that the drug can be used in single-photon emission computed tomography, are called iometopane I 123 (USAN
280px, "Samguk Sagi" Book 04. Silla's Records. In 512, Usan-guk(于山國)was Ulleungdo(鬱陵島)
Usan-guk, or the State of Usan, occupied Ulleung-do and the adjacent islands during the Korean Three Kingdoms period. According to th ...
) or iometopane 123I (INN
Inns are generally establishments or buildings where travelers can seek lodging, and usually, food and drink. Inns are typically located in the country or along a highway; before the advent of motorized transportation they also provided accommo ...
) 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 Ki values are attainable.
Uses
RTI-55 is mainly used in scientific research into the dopamine
Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic compound, organic chemical of the catecholamine and phenethylamine families. Dopamine const ...
reuptake transporter. Various radiolabelled
Isotopic labeling (or isotopic labelling) is a technique used to track the passage of an isotope (an atom with a detectable variation in neutron count) through a reaction, metabolic pathway, or cell. The reactant is 'labeled' by replacing specific ...
forms of RTI-55 (with different radioactive isotopes
Isotopes are two or more types of atoms that have the same atomic number (number of protons in their nuclei) and position in the periodic table (and hence belong to the same chemical element), and that differ in nucleon numbers (mass numbers) ...
of iodine
Iodine is a chemical element with the symbol I and atomic number 53. The heaviest of the stable halogens, it exists as a semi-lustrous, non-metallic solid at standard conditions that melts to form a deep violet liquid at , and boils to a vi ...
used depending on the application) are used in both humans and animals to map the distribution of dopamine transporter
The dopamine transporter (also dopamine active transporter, DAT, SLC6A3) is a membrane-spanning protein that pumps the neurotransmitter dopamine out of the synaptic cleft back into cytosol. In the cytosol, other transporters sequester the dop ...
s and serotonin transporter
The serotonin transporter (SERT or 5-HTT) also known as the sodium-dependent serotonin transporter and solute carrier family 6 member 4 is a protein that in humans is encoded by the SLC6A4 gene. SERT is a type of monoamine transporter protein tha ...
s in the brain
A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a v ...
. 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
Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms becom ...
, and some other conditions such as progressive supranuclear palsy
Progressive supranuclear palsy (PSP) is a late-onset degenerative disease involving the gradual deterioration and death of specific volumes of the brain. The condition leads to symptoms including loss of balance, slowing of movement, difficulty ...
.
Chemistry
RTI-55 is made as follows:
:
See also
* RTI-121
(–)-2β-Carboisopropoxy-3β-(4-iodophenyl)tropane (RTI-''4229''-121, IPCIT) is a stimulant drug used in scientific research, which was developed in the early 1990s. RTI-121 is a phenyltropane based, highly selective dopamine reuptake inhibitor ...
* RTI-229
RTI-229, also known as (–)-3β-(4-iodophenyl)tropane-2β-pyrrolidine carboxamide and RTI-''4229''-229, is a potent and long-lasting stimulant drug which was developed in the 1990s as part of a large group of related analogues from the phenylt ...
* RTI-352
RTI-352 is a phenyltropane that is used as a radiolabeling ligand for the DAT.
RTI-352 is a geometric isomer of RTI-55 (β-CIT).
Based on X-ray crystallography, this compound is in a tautomer
Tautomers () are structural isomers (constitut ...
* List of Phenyltropanes
References
{{Phenyltropanes
Iodoarenes
Tropanes
RTI compounds
Dopamine reuptake inhibitors
Stimulants
Sympathomimetic amines
Medical imaging
Neuroimaging