Iproheptine, also known as ''N''-isopropyl-1,5-dimethylhexylamine or ''N''-isopropyloctodrine and sold under the brand names Metron and Susat, is a

nasal decongestant A decongestant, or nasal decongestant, is a type of pharmaceutical drug that is used to relieve nasal congestion in the upper respiratory tract. The active ingredient in most decongestants is either pseudoephedrine or phenylephrine (the latter o ...

which has been marketed in

Japan Japan is an island country in East Asia. Located in the Pacific Ocean off the northeast coast of the Asia, Asian mainland, it is bordered on the west by the Sea of Japan and extends from the Sea of Okhotsk in the north to the East China Sea ...

. It is described as a

vasoconstrictor Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels, in particular the large arteries and small arterioles. The process is the opposite of vasodilation, the widening of blood vesse ...

and

antihistamine Antihistamines are drugs which treat allergic rhinitis, common cold, influenza, and other allergies. Typically, people take antihistamines as an inexpensive, generic (not patented) drug that can be bought without a prescription and provides ...

. The drug is available

over-the-counter Over-the-counter (OTC) drugs are medicines sold directly to a consumer without a requirement for a prescription from a healthcare professional, as opposed to prescription drugs, which may be supplied only to consumers possessing a valid pres ...

in Japan.

Pharmacology

Pharmacodynamics

Iproheptine is described as a

decongestant A decongestant, or nasal decongestant, is a type of pharmaceutical drug that is used to relieve nasal congestion in the upper respiratory tract. The active ingredient in most decongestants is either pseudoephedrine or phenylephrine (the latter o ...

, and

. Its

pharmacology Pharmacology is the science of drugs and medications, including a substance's origin, composition, pharmacokinetics, pharmacodynamics, therapeutic use, and toxicology. More specifically, it is the study of the interactions that occur betwee ...

was characterized in a series of several

preclinical studies In drug development, preclinical development (also termed preclinical studies or nonclinical studies) is a stage of research that begins before clinical trials (testing in humans) and during which important feasibility, iterative testing and dr ...

published in the 1960s. The drug was found to have

anticholinergic Anticholinergics (anticholinergic agents) are substances that block the action of the acetylcholine (ACh) neurotransmitter at synapses in the central nervous system, central and peripheral nervous system. These agents inhibit the parasympatheti ...

- and antihistamine-like effects that were described as more potent than those of

ephedrine Ephedrine is a central nervous system (CNS) stimulant and sympathomimetic agent that is often used to prevent hypotension, low blood pressure during anesthesia. It has also been used for asthma, narcolepsy, and obesity but is not the preferred ...

. It was said to have

hypotensive Hypotension, also known as low blood pressure, is a cardiovascular condition characterized by abnormally reduced blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood and is ...

and cardiac inhibitive actions that made it differ from other known alkylamine and arylalkylamine sympathomimetics. The effects of iproheptine on

blood vessel Blood vessels are the tubular structures of a circulatory system that transport blood throughout many Animal, animals’ bodies. Blood vessels transport blood cells, nutrients, and oxygen to most of the Tissue (biology), tissues of a Body (bi ...

pupil The pupil is a hole located in the center of the iris of the eye that allows light to strike the retina.Cassin, B. and Solomon, S. (1990) ''Dictionary of Eye Terminology''. Gainesville, Florida: Triad Publishing Company. It appears black becau ...

s, and saliva secretion were all said to be very weak. It produced

bronchodilation A bronchodilator or broncholytic (although the latter occasionally includes secretory inhibition as well) is a substance that dilates the bronchi and bronchioles, decreasing resistance in the respiratory airway and increasing airflow to the lung ...

vasoconstriction Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels, in particular the large arteries and small arterioles. The process is the opposite of vasodilation, the widening of blood vesse ...

, and

hemostasis In biology, hemostasis or haemostasis is a process to prevent and stop bleeding, meaning to keep blood within a damaged blood vessel (the opposite of hemostasis is hemorrhage). It is the first stage of wound healing. Hemostasis involves three ...

similarly to ephedrine or methoxyphenamine. Iproheptine showed no effect against

hexobarbital Hexobarbital or hexobarbitone, sold both in acid and sodium salt forms as Citopan, Evipan, and Tobinal, is a barbiturate derivative having hypnotic and sedative effects. It was used in the 1940s and 1950s as an agent for inducing anesthesia for s ...

-induced

sleep Sleep is a state of reduced mental and physical activity in which consciousness is altered and certain Sensory nervous system, sensory activity is inhibited. During sleep, there is a marked decrease in muscle activity and interactions with th ...

. Conversely, it showed an

antidepressant Antidepressants are a class of medications used to treat major depressive disorder, anxiety disorders, chronic pain, and addiction. Common side effects of antidepressants include Xerostomia, dry mouth, weight gain, dizziness, headaches, akathi ...

- or

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, ...

-like effect in the forced swim test (FST). Close analogues of iproheptine, such as

methylhexanamine Methylhexanamine (also known as methylhexamine, 1,3-dimethylamylamine, 1,3-DMAA, dimethylamylamine, and DMAA; trade names Forthane and Geranamine) is an indirect sympathomimetic drug invented and developed by Eli Lilly and Company and marketed ...

and

tuaminoheptane Tuaminoheptane (, ; brand names Heptin, Heptadrine, Tuamine; also known as tuamine and 2-aminoheptane) is a sympathomimetic agent and vasoconstrictor which was formerly used as a nasal decongestant. It is still used in France as a nasal decong ...

, are known to act as

norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic compound, organic chemical in the catecholamine family that functions in the brain and human body, body as a hormone, neurotransmitter and neuromodulator. The ...

and/or

dopamine releasing agent A dopamine releasing agent (DRA) is a type of drug which induces the release of dopamine in the Body (biology), body and/or brain. No binding selectivity, selective DRAs are currently known. However, non-selective DRAs, including norepinephrin ...

s by interacting with the

monoamine transporter Monoamine transporters (MATs) are proteins that function as integral Cell membrane, plasma-membrane Neurotransmitter transporter, transporters to regulate concentrations of extracellular monoamine neurotransmitters. The three major classes are se ...

s, and this is thought to underlie their sympathomimetic and stimulant effects.

Pharmacokinetics

In contrast to arylalkylamines like

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 ...

s and

tryptamine Tryptamine is an indolamine metabolite of the essential amino acid tryptophan. The chemical structure is defined by an indole—a fused benzene and pyrrole ring, and a 2-aminoethyl group at the second carbon (third aromatic atom, with the firs ...

s, iproheptine is not

metabolized Metabolism (, from ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cellular processes; the co ...

monoamine oxidase Monoamine oxidases (MAO) () are a family of enzymes that catalyze the oxidation of monoamines, employing oxygen to clip off their amine group. They are found bound to the outer membrane of mitochondria in most cell types of the body. The fi ...

(MAO).

Chemistry

Iproheptine, also known as ''N''-isopropyl-1,5-dimethylhexylamine or as ''N''-isopropyloctodrine, is an alkylamine and the ''N''-isopropyl

derivative In mathematics, the derivative is a fundamental tool that quantifies the sensitivity to change of a function's output with respect to its input. The derivative of a function of a single variable at a chosen input value, when it exists, is t ...

octodrine Octodrine, also known as dimethylhexylamine (DMHA) and sold under the brand name Vaporpac among others, is a sympathomimetic and stimulant medication that was formerly used in the treatment of hypotension (low blood pressure). It has been stud ...

(2-amino-6-methylheptane or 1,5-dimethylhexylamine (1,5-DMHA)). Aside from octodrine, it is also closely structurally related to other alkylamines, including

1,3-dimethylbutylamine 1,3-Dimethylbutylamine (1,3-DMBA, dimethylbutylamine, DMBA, 4-amino-2-methylpentane, or AMP), is a stimulant drug structurally related to methylhexanamine where a butyl group replaces the pentyl group. The compound is an aliphatic amine. The ...

(1,3-DMBA), 1,4-dimethylamylamine (1,4-DMAA), heptaminol (2-methyl-6-amino-2-heptanol), isometheptene (2-methyl-6-methylamino-2-heptene),

(1,3-dimethylamylamine (1,3-DMAA)), and

(tuamine; 2-aminoheptane or 1-methylhexylamine). Iproheptine shows structural similarity to what would be 3- or 4-methyl-''N''-isopropylamphetamine, but with the equivalent of the phenyl ring open and incomplete (i.e., missing two

carbon Carbon () is a chemical element; it has chemical symbol, symbol C and atomic number 6. It is nonmetallic and tetravalence, tetravalent—meaning that its atoms are able to form up to four covalent bonds due to its valence shell exhibiting 4 ...

atom Atoms are the basic particles of the chemical elements. An atom consists of a atomic nucleus, nucleus of protons and generally neutrons, surrounded by an electromagnetically bound swarm of electrons. The chemical elements are distinguished fr ...

s, saturated, and the carbons not connected to form a ring). The predicted log P ( XLogP3) of iproheptine is 3.6.

History

Iproheptine was first described in the

scientific literature Scientific literature encompasses a vast body of academic papers that spans various disciplines within the natural and social sciences. It primarily consists of academic papers that present original empirical research and theoretical ...

by 1960 and was first

patent A patent is a type of intellectual property that gives its owner the legal right to exclude others from making, using, or selling an invention for a limited period of time in exchange for publishing an sufficiency of disclosure, enabling discl ...

ed by 1962. It remained marketed in

in 2004.

Society and culture

Names

''Iproheptine'' is the generic name of the drug and its . In the case of the

hydrochloride In chemistry, a hydrochloride is an acid salt resulting, or regarded as resulting, from the reaction of hydrochloric acid with an organic base (e.g. an amine). An alternative name is chlorhydrate, which comes from French. An archaic alternati ...

salt In common usage, salt is a mineral composed primarily of sodium chloride (NaCl). When used in food, especially in granulated form, it is more formally called table salt. In the form of a natural crystalline mineral, salt is also known as r ...

, its generic name is ''iproheptine hydrochloride'' and this is its . The drug is marketed under the brand names ''Metron'' and ''Susat'' (both as the hydrochloride salt).

Availability

Iproheptine appears to have been marketed only in

. It is available

in this country.

References

{{Decongestants Decongestants Drugs with unknown mechanisms of action Isopropylamino compounds Secondary amines Sympathomimetics Vasoconstrictors