Tripelennamine is psychoactive drug

Psychoactive drug

A psychoactive drug, psychopharmaceutical, or psychotropic is a chemical substance that crosses the blood–brain barrier and acts primarily upon the central nervous system where it affects brain function, resulting in changes in perception, mood, consciousness, cognition, and behavior...

 and member of the pyridine

Pyridine

Pyridine is a basic heterocyclic organic compound with the chemical formula C5H5N. It is structurally related to benzene, with one C-H group replaced by a nitrogen atom...

 and ethylenediamine classes that is used as an antipruritic

Antipruritic

Antipruritics, also known as anti-itch drugs, are medications that inhibit the itching that is often associated with sunburns, allergic reactions, eczema, psoriasis, chickenpox, fungal infections, insect bites and stings like those from mosquitoes, fleas, and mites, and contact dermatitis and...

 and first-generation antihistamine

Antihistamine

An H1 antagonist is a histamine antagonist of the H1 receptor that serves to reduce or eliminate effects mediated by histamine, an endogenous chemical mediator released during allergic reactions...

. It can be used in the treatment of asthma

Asthma

Asthma is the common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include wheezing, coughing, chest tightness, and shortness of breath...

, hay fever

Hay Fever

Hay Fever is a comic play written by Noël Coward in 1924 and first produced in 1925 with Marie Tempest as the first Judith Bliss. Laura Hope Crews played the role in New York...

, rhinitus and urticaria

Urticaria

Urticaria is a kind of skin rash notable for pale red, raised, itchy bumps. Hives is frequently caused by allergic reactions; however, there are many non-allergic causes...

, but is now less common as it has been replaced by newer antihistamines.

History

Tripelennamine was first synthesized by Carl Djerassi

Carl Djerassi

Carl Djerassi is an Austrian-American chemist, novelist, and playwright best known for his contribution to the development of the first oral contraceptive pill . Djerassi is emeritus professor of chemistry at Stanford University.He participated in the invention in 1951, together with Mexican Luis E...

, working in the laboratory of Charles Huttrer at Ciba, shortly after Djerassi got his B.S

Bachelor of Science

A Bachelor of Science is an undergraduate academic degree awarded for completed courses that generally last three to five years .-Australia:In Australia, the BSc is a 3 year degree, offered from 1st year on...

. It was his first patent

Patent

A patent is a form of intellectual property. It consists of a set of exclusive rights granted by a sovereign state to an inventor or their assignee for a limited period of time in exchange for the public disclosure of an invention....

.

Pharmacology

Tripelennamine acts primarily as an antihistamine

Antihistamine

An H1 antagonist is a histamine antagonist of the H1 receptor that serves to reduce or eliminate effects mediated by histamine, an endogenous chemical mediator released during allergic reactions...

, or H₁

H1 receptor

The H1 receptor is a histamine receptor belonging to the family of Rhodopsin like G-protein-coupled receptors. This receptor, which is activated by the biogenic amine histamine, is expressed throughout the body, to be specific, in smooth muscles, on vascular endothelial cells, in the heart, and in...

 receptor

Receptor (biochemistry)

In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...

 antagonist

Receptor antagonist

A receptor antagonist is a type of receptor ligand or drug that does not provoke a biological response itself upon binding to a receptor, but blocks or dampens agonist-mediated responses...

. It has little to no anticholinergic

Anticholinergic

An anticholinergic agent is a substance that blocks the neurotransmitter acetylcholine in the central and the peripheral nervous system. An example of an anticholinergic is dicycloverine, and the classic example is atropine....

 activity. In addition to its antihistamine properties, tripelennamine also acts as a weak serotonin reuptake inhibitor (SRI) and dopamine reuptake inhibitor

Dopamine reuptake inhibitor

A dopamine reuptake inhibitor is a type of drug that acts as a reuptake inhibitor for the neurotransmitter dopamine by blocking the action of the dopamine transporter...

 (DRI). Because of its SRI properties, tripelennamine was used as the basis for the development of the selective serotonin reuptake inhibitor

Selective serotonin reuptake inhibitor

Selective serotonin re-uptake inhibitors or serotonin-specific reuptake inhibitor are a class of compounds typically used as antidepressants in the treatment of depression, anxiety disorders, and some personality disorders. The efficacy of SSRIs is disputed...

 (SSRI) fluvoxamine

Fluvoxamine

Fluvoxamine is an antidepressant which functions as a selective serotonin reuptake inhibitor . Fluvoxamine was first approved by the U.S. Food and Drug Administration in 1993 for the treatment of obsessive compulsive disorder . Fluvoxamine CR is approved to treat social anxiety disorder...

 (Luvox). Additionally, due to its DRI properties, it is occasionally abused as a recreational drug (see below).

Side effects

Tripelennamine is mildly sedating

Sedative

A sedative or tranquilizer is a substance that induces sedation by reducing irritability or excitement....

. Other side effects can include gastrointestinal irritation, dry mouth, nausea

Nausea

Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...

, and dizziness

Dizziness

Dizziness refers to an impairment in spatial perception and stability. The term is somewhat imprecise. It can be used to mean vertigo, presyncope, disequilibrium, or a non-specific feeling such as giddiness or foolishness....

.

Recreational use

Tripelennamine is sometimes abused recreationally in combination with the synthetic opioid

Opioid

An opioid is a psychoactive chemical that works by binding to opioid receptors, which are found principally in the central and peripheral nervous system and the gastrointestinal tract...

 pentazocine

Pentazocine

Pentazocine is a synthetically prepared prototypical mixed agonist-antagonist narcotic drug of the benzomorphan class of opioids used to treat moderate to moderately severe pain...

 ("T's & Blues"), or morphine

Morphine

Morphine is a potent opiate analgesic medication and is considered to be the prototypical opioid. It was first isolated in 1804 by Friedrich Sertürner, first distributed by same in 1817, and first commercially sold by Merck in 1827, which at the time was a single small chemists' shop. It was more...

 ("Blue Velvet"), by preparing an injection containing both agents; tripelennamine is also used with cough syrups and analgesic solid preparations containing opioids including codeine

Codeine

Codeine or 3-methylmorphine is an opiate used for its analgesic, antitussive, and antidiarrheal properties...

, propoxyphene (Darvocet), dextropropoxyphene

Dextropropoxyphene

Dextropropoxyphene, manufactured by Eli Lilly and Company, is an analgesic in the opioid category. It is intended to treat mild pain and has, in addition, anti-tussive and local anesthetic effects. It has been taken off the market in Europe and the US due to concerns of fatal overdoses and...

 (Darvocet-N, Di-Gesic), hydrocodone

Hydrocodone

Hydrocodone or dihydrocodeinone is a semi-synthetic opioid derived from either of two naturally occurring opiates: codeine and thebaine. It is an orally active narcotic analgesic and antitussive...

 (Vicodin, Xodol, Lortab), ethylmorphine

Ethylmorphine

Ethylmorphine is an opiate narcotic analgesic .Ethylmorphine was invented in Germany at Merck in 1884 and was used as a weaker alternative to heroin for all indications. Chemically, ethylmorphine is a morphine molecule with a -25 group substituted for the aromatic 3- group...

 (Dionine, codethyline), paregoric

Paregoric

Paregoric, or camphorated tincture of opium, also known as tinctura opii camphorata, is a medication known for its antidiarrheal, antitussive, and analgesic properties.-History:...

, benzylmorphine

Benzylmorphine

Benzylmorphine is a semi-synthetic opiate narcotic introduced to the international market in 1896 and that of the United States very shortly thereafter...

, tramadol

Tramadol

Tramadol hydrochloride is a centrally acting synthetic opioid analgesic used in treating moderate pain. The drug has a wide range of applications, including treatment for restless legs syndrome and fibromyalgia...

 (Ultram, Ultracet, Rybix, Tramal), oxycodone

Oxycodone

Oxycodone is an opioid analgesic medication synthesized from opium-derived thebaine. It was developed in 1916 in Germany, as one of several new semi-synthetic opioids in an attempt to improve on the existing opioids: morphine, diacetylmorphine , and codeine.Oxycodone oral medications are generally...

 (Percocet, Roxicet, Tylox, OxyContin, OxyNorm), and dihydrocodeine

Dihydrocodeine

Dihydrocodeine, also called DHC, Drocode, Paracodeine and Parzone and known by the brand names of Synalgos DC, Panlor DC, Panlor SS, Contugesic, New Bron Solution-ACE, Huscode, Drocode, Paracodin, Codidol, Didor Continus, Dicogesic, Codhydrine, Dekacodin, DH-Codeine,...

 and its derivatives. hydromorphone

Hydromorphone

Hydromorphone, a more common synonym for dihydromorphinone, commonly a hydrochloride is a very potent centrally-acting analgesic drug of the opioid class. It is a derivative of morphine, to be specific, a hydrogenated ketone thereof and, therefore, a semi-synthetic drug...

 (Palladone, dilaudid), oxymorphone

Oxymorphone

Oxymorphone or 14-Hydroxydihydromorphinone is a powerful semi-synthetic opioid analgesic first developed in Germany circa 1914, patented in the USA by Endo Pharmaceuticals in 1955 and introduced to the United States market in January 1959 and other countries around the same time...

 (Opana, Numorphan), and solid forms of methadone

Methadone

Methadone is a synthetic opioid, used medically as an analgesic and a maintenance anti-addictive for use in patients with opioid dependency. It was developed in Germany in 1937...

 (Symoron, Pinadone) by either method.

It is dangerous to combine an opiate with a sedating antihistamine via injection, although the use of antihistamines (usually by mouth) to reduce opioid requirements for pain relief is a well-known practice, which is done under medical supervision with tripelennamine, as well as hydroxyzine

Hydroxyzine

Hydroxyzine is a first-generation antihistamine of the diphenylmethane and piperazine classes. It was first synthesized by Union Chimique Belge in 1956 and was marketed by Pfizer in the United States later the same year, and is still in widespread use today....

, cyclizine

Cyclizine

Cyclizine is an antihistamine drug used to treat nausea, vomiting and dizziness associated with motion sickness, vertigo and post-operatively following administration of general anaesthesia and opioids.-Indications:...

, promethazine

Promethazine

Promethazine is a first-generation antihistamine of the phenothiazine family. The drug has anti-motion sickness, antiemetic, and anticholinergic effects, as well as a strong sedative effect and in some countries is prescribed for insomnia when benzodiazepines are contraindicated...

, diphenhydramine

Diphenhydramine

Diphenhydramine hydrochloride is a first-generation antihistamine possessing anticholinergic, antitussive, antiemetic, and sedative properties which is mainly used to treat allergies. Like most other first-generation antihistamines, the drug also has a powerful hypnotic effect, and for this reason...

, phenindamine

Phenindamine

Phenindamine is an antihistamine and anticholinergic closely related to cyproheptadine which is used to treat symptoms of the common cold and allergies, such as sneezing, itching, rashes, and hives. Its efficacy against some symptoms of opioid withdrawal was researched in the 1950s and 1960s in a...

, orphenadrine

Orphenadrine

Orphenadrine is an anticholinergic drug of the ethanolamine antihistamine class with prominent CNS and peripheral actions used to treat painful muscle spasms, other similar conditions, as well as the treatment...

, meclozine

Meclozine

Meclozine is an antihistamine considered to be an antiemetic. It is sold under the brand names Bonine, Bonamine, Antivert, Postafen, Sea Legs, and Dramamine . Emesafene is a combination of meclozine and pyridoxine...

, chlorpheniramine, cyproheptadine

Cyproheptadine

Cyproheptadine , sold under the brand name Periactin, is a first-generation antihistamine with additional anticholinergic, antiserotonergic, and local anesthetic properties.- Indications :...

 and others; this method is doubly useful when used with opioids which release a great deal of histamine when administered and therefore cause itching, redness of skin and other histamine-related effects.

Like many of the first-generation antihistamines of the ethanolamine and alkylamine classes, tripelennamine and other members of its chemical class (ethylenediamines) produces a marginal to moderate euphoria; triepelennamine has a euphoriant effect with a relatively rapid onset and up to eight hours in duration. The ethylenediamine antihistamines rank between the ethanolamines and the alkylamines in this effect—somewhat weaker than orphenadrine

Orphenadrine

Orphenadrine is an anticholinergic drug of the ethanolamine antihistamine class with prominent CNS and peripheral actions used to treat painful muscle spasms, other similar conditions, as well as the treatment...

 and phenyltoloxamine

Phenyltoloxamine

Phenyltoloxamine is an antihistamine with sedative and analgesic effects. It is a member of the ethanolamine class of antihistaminergic agents and an anticholinergic.-Common use:...

, a bit stronger than brompheniramine

Brompheniramine

Brompheniramine , commonly marketed as its salt brompheniramine maleate is an antihistamine drug of the propylamine class...

 and roughly comparable to dexchlorpheniramine

Dexchlorpheniramine

Dexchlorpheniramine is an antihistamine with anticholinergic properties used to treat allergic conditions such as hay fever or urticaria...

 and triprolidine

Triprolidine

Triprolidine is an over-the-counter antihistamine with anticholinergic properties. It is used to combat the symptoms associated with allergies and is sometimes combined with other cold medications designed to provide general relief for flu-like symptoms. Like many over-the-counter antihistamines,...

.

An episode of Joe Frank

Joe Frank

Joe Frank is an American radio personality, known best for his often philosophical, humorous, surrealist, and sometimes absurd monologues and radio dramas.-Early life:...

's NPR radio show, Somewhere Out There, was devoted to Pyribenzamine and its recreational devotees.

Chemistry

Tripelennamine, N-benzyl-N′,N′-dimethyl-N-2-pyridylethylenediamine, is synthesized by reacting 2-benzylaminopyrridine with 2-dimethylaminoethylchloride in the presence of sodium amide

Sodium amide

Sodium amide, commonly called sodamide, is the chemical compound with the formula NaNH2. This solid, which is dangerously reactive toward water, is white when pure, but commercial samples are typically gray due to the presence of small quantities of metallic iron from the manufacturing process...

. 2-Benzylaminopyrridine, in turn, can be easily synthesized by reduction of a Schiff base

Schiff base

A Schiff base, named after Hugo Schiff, is a compound with a functional group that contains a carbon-nitrogen double bond with the nitrogen atom connected to an aryl or alkyl group, not hydrogen....

, synthesized by condensation of 2-aminopyrridine with benzaldehyde.

• Ch.P. Huttrer, C. Gjerassi, C.R. Scholz, (1946).
• R.J. Horclois, (1950).