Tetrahydroisoquinoline (TIQ or THIQ), also known as AMPH-CR, is an

organic compound Some chemical authorities define an organic compound as a chemical compound that contains a carbon–hydrogen or carbon–carbon bond; others consider an organic compound to be any chemical compound that contains carbon. For example, carbon-co ...

with the chemical formula C₉H₁₁N. Classified as a

secondary amine In chemistry, amines (, ) are organic compounds that contain carbon-nitrogen bonds. Amines are formed when one or more hydrogen atoms in ammonia are replaced by alkyl or aryl groups. The nitrogen atom in an amine possesses a lone pair of elec ...

, it is derived from

isoquinoline Isoquinoline is an individual chemical specimen - a heterocyclic aromatic organic compound - as well as the name of a family of many thousands of natural plant alkaloids, any one of which might be referred to as "an isoquinoline". It is a struc ...

by hydrogenation. It is a colorless viscous liquid that is miscible with most organic solvents. The tetrahydroisoquinoline skeleton is encountered in a number of bioactive compounds and drugs.

Pharmacology

THIQ is a conformationally restrained (CR) or cyclized analogue of

β-phenethylamine Phenethylamine (PEA) is an organic compound, natural monoamine alkaloid, and trace amine, which acts as a central nervous system stimulant in humans. In the brain, phenethylamine regulates monoamine neurotransmission by binding to trace ami ...

and

amphetamine Amphetamine (contracted from Alpha and beta carbon, alpha-methylphenethylamine, methylphenethylamine) is a central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, an ...

and is also known as AMPH-CR. In contrast to amphetamine however, THIQ fails to substitute for

dextroamphetamine Dextroamphetamine (international nonproprietary name, INN: dexamfetamine) is a potent central nervous system (CNS) stimulant and enantiomer of amphetamine that is used in the treatment of attention deficit hyperactivity disorder (ADHD) and narc ...

in rodent

drug discrimination Drug discrimination (DD) is a technique in behavioral neuroscience used to evaluate the discriminative stimulus properties or interoceptive cues of psychoactive drugs. In drug discrimination, a subject is trained on a training drug, and then i ...

tests, suggesting that it lacks

stimulant 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, ...

effects. Similar findings have been made for other tetrahydroisoquinoline analogues of

psychoactive A psychoactive drug, psychopharmaceutical, mind-altering drug, consciousness-altering drug, psychoactive substance, or psychotropic substance is a chemical substance that alters psychological functioning by modulating central nervous system acti ...

phenethylamines, for instance

DOM-CR DOM-CR, or DOM/CR, an acronym of "DOM-conformationally restrained", is a tetrahydroisoquinoline (THIQ) and cyclized phenethylamine related to the psychedelics DOM and 2C-D. It is a cyclized THIQ analogue of DOM and 2C-D. DOM-CR shows more than ...

. In any case, THIQ does substitute for

TDIQ TDIQ, also known as MDTHIQ or MDA-CR, is a tetrahydroisoquinoline drug used in scientific research, which has anxiolytic and anorectic effects in animals. It has an unusual effects profile in animals, with the effects generalising to cocaine and ...

(MDTIQ), a selective α₂-adrenergic receptor

ligand In coordination chemistry, a ligand is an ion or molecule with a functional group that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's el ...

, indicating that it is not pharmacologically inactive.

Reactions

As a secondary amine, tetrahydroisoquinoline has weakly basic properties and forms salts with strong acids. It can be dehydrogenated to give isoquinoline and hydrogenated to

decahydroisoquinoline Decahydroisoquinoline is a nitrogen-containing heterocycle with the chemical formula . It is the saturated form of isoquinoline. Decahydroisoquinoline can be formed by the hydrogenation of isoquinoline or tetrahydroisoquinoline. Isomers There ...

. Like other secondary amines, tetrahydroisoquinoline can be oxidized to the corresponding

nitrone In organic chemistry, a nitrone is a functional group consisting of an Amine oxide, ''N''-oxide of an imine. The general structure is , where R3 is not a hydrogen. Their primary application is Chemical Intermediate, intermediates in chemical syn ...

using

hydrogen peroxide Hydrogen peroxide is a chemical compound with the formula . In its pure form, it is a very pale blue liquid that is slightly more viscosity, viscous than Properties of water, water. It is used as an oxidizer, bleaching agent, and antiseptic, usua ...

, catalyzed by

selenium dioxide Selenium dioxide is the chemical compound with the formula SeO2. This colorless solid is one of the most frequently encountered compounds of selenium. It is used in making specialized glasses as well as a reagent in organic chemistry. Properties ...

Toxicology

Tetrahydroisoquinoline derivatives may be formed in the body as metabolites of some drugs, and this was once thought to be involved in the development of

alcoholism Alcoholism is the continued drinking of alcohol despite it causing problems. Some definitions require evidence of dependence and withdrawal. Problematic use of alcohol has been mentioned in the earliest historical records. The World He ...

. This theory has now been discredited and is no longer generally accepted by the scientific community, but endogenous production of neurotoxic tetrahydroisoquinoline derivatives such as

norsalsolinol Norsalsolinol is a tetrahydroisoquinoline that is produced naturally in the body through the metabolism of dopamine. It has been shown to be a selective dopaminergic neurotoxin, and has been suggested as a possible cause of neurodegenerative condi ...

continue to be investigated as possible causes for some conditions such as

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 ...

Tetrahydroisoquinolines

The tetrahydroisoquinoline skeleton is present in a number of drugs, such as

tubocurarine Tubocurarine (also known as ''d''-tubocurarine or DTC) is a toxic benzylisoquinoline alkaloid historically known for its use as an arrow poison. In the mid-1900s, it was used in conjunction with an anesthetic to provide skeletal muscle relaxat ...

, one of the

quaternary ammonium muscle relaxants The Quaternary ( ) is the current and most recent of the three periods of the Cenozoic Era in the geologic time scale of the International Commission on Stratigraphy (ICS), as well as the current and most recent of the twelve periods of the P ...

. Drugs based on 4-substituted tetrahydroisoquinolines include

nomifensine Nomifensine, formerly sold under the brand names Merital and Alival, is a norepinephrine–dopamine reuptake inhibitor (NDRI) drug that was developed in the 1960s by Hoechst AG (now Sanofi-Aventis), who then test marketed it in the United States ...

and

diclofensine Diclofensine (Ro 8-4650) was developed by Hoffmann-La Roche in the 1970s in the search for a new antidepressant. It was found that the (''S'')-isomer was responsible for activity. Diclofensine is a stimulant drug which acts as a triple monoamin ...

. They can be prepared by ''N''-alkylation of benzyl amines with halo

acetophenone Acetophenone is the organic compound with the formula C6H5C(O)CH3. It is the simplest aromatic ketone. This colorless, viscous liquid is a precursor to useful resins and fragrances. Production Acetophenone is formed as a byproduct of the cumene ...

s. Naturally occurring tetrahydroisoquinolines include cheryllinecherylline
/ref> and latifine. Esproquin, which shows hypotensive activity by virtue of its α-adrenergic blocking properties, is made from THIQ.

References

{{Phenethylamines

Pharmacology

Reactions

Toxicology

Tetrahydroisoquinolines

See also

References