Tripelennamine

Tripelennamine (sold as Pyribenzamine by Novartis) is psychoactive drug and member of the pyridine and ethylenediamine chemical classes that is used as an antipruritic and first-generation antihistamine. It can be used in the treatment of asthma, hay fever, rhinitus and urticaria, but is now less common as it has been replaced by newer antihistamines.

History

Tripelennamine was first synthesized by Carl Djerassi, working in the laboratory of Charles Huttrer at Ciba, shortly after Djerassi got his B.S. It was his first patent.

Pharmacology

Tripelennamine functions primarily as an antihistamine, or H₁ receptor antagonist. It is also mildly anticholinergic, or muscarinic acetylcholine receptor antagonistic. Notably, in addition to its antihistamine and anticholinergic effects, tripelennamine also functions as a weak serotonin reuptake inhibitor (SRI) and dopamine reuptake inhibitor (DRI). Because of its SRI properties, tripelennamine was used as the basis for the development of the selective serotonin reuptake inhibitor (SSRI) fluvoxamine (Luvox). In addition, due to its DRI properties, it is occasionally abused as a recreational drug (see below).

Side effects

Tripelennamine is mildly sedating. Other side effects can include gastrointestinal irritation, dry mouth, nausea, and dizziness.

Recreational use

Tripelennamine is sometimes abused recreationally in combination with the synthetic opioid pentazocine ("T's & Blues"), or morphine ("Blue Velvet"), by preparing an injection containing both agents; tripelennamine is also used with cough syrups and analgesic solid preparations containing opioids including codeine, propoxyphene, dextropropoxyphene, hydrocodone, ethylmorphine (Dionine, codethyline), paregoric, benzylmorphine, tramadol (Tramal, Tramagetic), oxycodone (OxyContin, OxyNorm), and dihydrocodeine and its derivatives. hydromorphone (Palladone, dilaudid), oxymorphone (Opana, Numorphan), and solid forms of methadone (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, cyclizine, promethazine, diphenhydramine, phenindamine, orphenadrine, meclozine, chlorpheniramine, cyproheptadine 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 and phenyltoloxamine, a bit stronger than brompheniramine and roughly comparable to dexchlorpheniramine and triprolidine.

An episode of Joe Frank'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. 2-Benzylaminopyrridine, in turn, can be easily synthesized by reduction of a Schiff base, synthesized by condensation of 2-aminopyrridine with benzaldehyde. Ch.P. Huttrer, C. Gjerassi, C.R. Scholz, (1946). R.J. Horclois, (1950).

References

Category:H1 receptor antagonists Category:Pyridines