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. This research has spanned beyond the last couple decade ...
-based
psychostimulant
Stimulants (also known as central nervous system stimulants, or psychostimulants, or colloquially as uppers) are a class of drugs that increase alertness. They are used for various purposes, such as enhancing attention, motivation, cognition ...
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 dop ...
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 methylecgonidi ...
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 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; it has symbol I and atomic number 53. The heaviest of the stable halogens, it exists at standard conditions as a semi-lustrous, non-metallic solid that melts to form a deep violet liquid at , and boils to a vi ...
atom is radioiodine
There are 40 known isotopes of iodine (53I) from 108I to 147I; 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 16.14 million ye ...
so that the drug can be used in single-photon emission computed tomography
Single-photon emission computed tomography (SPECT, or less commonly, SPET) is a nuclear medicine tomography, tomographic imaging technique using gamma rays. It is very similar to conventional nuclear medicine planar imaging using a gamma camera ...
, 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 t ...
) 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 accomm ...
) and iometopane I 125 (USAN) or iometopane 125I (INN). The 123I and 125I isotopes are favored because they are very-high-energy γ-ray
A gamma ray, also known as gamma radiation (symbol ), is a penetrating form of electromagnetic radiation arising from high energy interactions like the radioactive decay of atomic nuclei or astronomical events like solar flares. It consists o ...
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 chemical of the catecholamine and phenethylamine families. It is an amine synthesized ...
reuptake transporter. Various radiolabelled
A radioactive tracer, radiotracer, or radioactive label is a synthetic derivative of a natural compound in which one or more atoms have been replaced by a radionuclide (a radioactive atom). By virtue of its radioactive decay, it can be used to exp ...
forms of RTI-55 (with different radioactive isotopes
Isotopes are distinct nuclear species (or ''nuclides'') of the same chemical element. They 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), but ...
of iodine
Iodine is a chemical element; it has symbol I and atomic number 53. The heaviest of the stable halogens, it exists at standard conditions as a semi-lustrous, non-metallic solid 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 (DAT, also sodium-dependent dopamine transporter) is a membrane-spanning protein coded for in humans by the ''SLC6A3'' gene (also known as ''DAT1''), that pumps the neurotransmitter dopamine out of the synaptic cleft ba ...
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 t ...
s in the brain
The brain is an organ (biology), organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It consists of nervous tissue and is typically located in the head (cephalization), usually near organs for ...
. 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 neurodegenerative disease primarily of the central nervous system, affecting both motor system, motor and non-motor systems. Symptoms typically develop gradually and non-motor issues become ...
, and some other conditions such as progressive supranuclear palsy
Progressive supranuclear palsy (PSP) is a late-onset neurodegenerative disease involving the gradual deterioration and death of specific volumes of the brain, linked to 4-repeat tau pathology. The condition leads to symptoms including Balance di ...
.
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
In chemistry, tautomers () are structural isomers ...
* List of Phenyltropanes
References
{{Phenyltropanes
4-Iodophenyl compounds
Tropanes
RTI compounds
Dopamine reuptake inhibitors
Stimulants
Sympathomimetic amines
Medical imaging
Neuroimaging
Methyl esters