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 Stimulants (also often referred to as psychostimulants or colloquially as uppers) is an overarching term that covers many drugs including those that increase activity of the central nervous system and the body, drugs that are pleasurable and inv ...

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 do ...

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, 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. 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 structural analog, analog of cocaine that acts as a stimulant. Semi-synthesis of this compound is dependent upon the availability of cocaine starting material. A ...

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 is ...

forms of RTI-55, in which the

iodine Iodine is a chemical element with the Symbol (chemistry), 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 , ...

atom is radioiodine 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 tomographic imaging technique using gamma rays. It is very similar to conventional nuclear medicine planar imaging using a gamma camera (that is, ...

, are called iometopane I 123 ( USAN) 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 K_i 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. Dopamine constitutes about 8 ...

reuptake transporter. Various radiolabelled forms of RTI-55 (with different radioactive isotopes of

used depending on the application) are used in both humans and animals to map the distribution of dopamine transporters 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 th ...

s in the

brain The brain is an 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 special ...

. 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.

Chemistry

RTI-55 is made as follows: : RTI-55 Syntheses

References

{{Phenyltropanes Iodoarenes Tropanes RTI compounds Dopamine reuptake inhibitors Stimulants Sympathomimetic amines Medical imaging Neuroimaging

Uses

Chemistry

See also

References