H1 antagonists, also called H1 blockers, are a class of medications that block the action of histamine at the H1 receptor, helping to relieve allergic reactions. Agents where the main therapeutic effect is mediated by negative modulation of histamine receptors are termed antihistamines; other agents may have antihistaminergic action but are not true antihistamines.
Clemastine, also known as meclastin, is an ethanolamine-derivative, first generation histamine H1 antagonist (antihistamine) with anticholinergic properties (drying) and sedative side effects. Unlike many second or third generation antihistamines, clemastine, like all first generation antihistamines, is sedating.
Levocetirizine, sold under the brand name Xyzal among others, is an antihistamine used for the treatment of allergic rhinitis and long term hives of unclear cause. It is less sedating than older antihistamines. It is taken by mouth.
Fluacizine, sold under the brand name Phtorazisin, is a tricyclic antidepressant (TCA) of the phenothiazine group which is or was marketed in Russia. Unlike other phenothiazines, fluacizine is not an antipsychotic, and can actually reverse catalepsy and extrapyramidal symptoms induced by antidopaminergic agents like antipsychotics, reserpine, and tetrabenazine as well as potentiate amphetamine-induced stereotypy. It is known to act as a norepinephrine reuptake inhibitor, antihistamine, and anticholinergic. The drug was developed in the 1960s and was marketed in the 1970s. It is the trifluoromethyl analogue of chloracizine.
Mesoridazine(Serentil) is a piperidine neuroleptic drug belonging to the class of drugs called phenothiazines, used in the treatment of schizophrenia. It is a metabolite of thioridazine. The drug's name is derived from the methylsulfoxy and piperidine functional groups in its chemical structure.
Propiomazine is an antihistamine blocking H1 receptors. It is used to treat insomnia, and to produce sleepiness or drowsiness and to relieve anxiety before or during surgery or other procedures and in combination with analgetics also during labor. Propiomazine is a phenothiazine, but is not used as a neuroleptic because it does not block dopamine receptors well.
Oxatomide, sold under the brand name Tinset among others, is a first-generation antihistamine of the diphenylmethylpiperazine family which is marketed in Europe, Japan, and a number of other countries. It was discovered at Janssen Pharmaceutica in 1975. Oxatomide lacks any anticholinergic effects. In addition to its H1 receptor antagonism, it also possesses antiserotonergic activity similarly to hydroxyzine.
Methapyrilene is an antihistamine and anticholinergic of the pyridine chemical class which was developed in the early 1950s. It was sold under the trade names Co-Pyronil and Histadyl EC. It has relatively strong sedative effects, to the extent that its primary use was as a medication for insomnia rather than for its antihistamine action. Together with scopolamine, it was the main ingredient in Sominex, Nytol, and Sleep-Eze. It also provided the sedative component of Excedrin PM. All of these products were reformulated in the late 1970s when methapyrilene was demonstrated to cause liver cancer in rats when given chronically.
Tricyclics are chemical compounds that contain three interconnected rings of atoms.
Azaperone is a pyridinylpiperazine and butyrophenone neuroleptic drug with sedative and antiemetic effects, which is used mainly as a tranquilizer in veterinary medicine. It is uncommonly used in humans as an antipsychotic drug.
Cloperastine (INN) or cloperastin, also known as cloperastine hydrochloride (JAN) (brand names Hustazol, Nitossil, Seki) and cloperastine fendizoate (or hybenzoate), is an antitussive and antihistamine that is marketed as a cough suppressant in Japan, Hong Kong, and in some European countries. It was first introduced in 1972 in Japan, and then in Italy in 1981. The precise mechanism of action of cloperastine is not fully clear, but several different biological activities have been identified for the drug, of which include: ligand of the σ1 receptor (Ki = 20 nM) (likely an agonist), GIRK channel blocker (described as "potent"), antihistamine (Ki = 3.8 nM for the H1 receptor), and anticholinergic. It is thought that the latter two properties contribute to side effects, such as sedation and somnolence, while the former two may be involved in or responsible for the antitussive efficacy of cloperastine.
Pyrrobutamine is an antihistamine and anticholinergic.
Phenindamine is an antihistamine and anticholinergic closely related to cyproheptadine. It was developed by Hoffman-La Roche in the late 1940s. It 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 number of countries; William S. Burroughs' book Junkie mentions this technique. Like many other first-generation antihistamines, phenindamine has useful potentiating effects on many narcotic analgesics and is even more useful with those opioids which release histamine when in the body.
Thozalinone (USAN) is a psychostimulant that has been used as an antidepressant in Europe. It has also been trialed as an anorectic. Thozalinone is described as a "dopaminergic stimulant", and likely acts via inducing the release of dopamine and to a minimal extent norepinephrine; similar to analogue pemoline, it is seemingly devoid of abuse potential unlike common psychostimulants that increase catecholamines.
Oxypertine is an antipsychotic used in the treatment of schizophrenia. It was also evaluated for the treatment of anxiety at a dosage of 20 mg per day. Chemically, it is an indole and phenylpiperazine derivative. Like reserpine and tetrabenazine, oxypertine depletes catecholamines, though not serotonin, possibly underlying its neuroleptic efficacy. Its structure is similar to solypertine and milipertine.
Prothipendyl, also known as azaphenothiazine or phrenotropin, is an anxiolytic, antiemetic, and antihistamine of the azaphenothiazine group which is marketed in Europe and is used to treat anxiety and agitation in psychotic syndromes. It differs from promazine only by the replacement of one carbon atom with a nitrogen atom in the tricyclic ring system. Prothipendyl is said to not possess antipsychotic effects, and in accordance, appears to be a weaker dopamine receptor antagonist than other phenothiazines.
Piperoxan, also known as benodaine, is a drug which was the very first antihistamine to be discovered. This compound, derived from benzodioxan, was prepared in the early 1930s by Daniel Bovet and Ernest Fourneau at the Pasteur Institute in France. Formerly investigated by Fourneau as an α-adrenergic-blocking agent, they demonstrated that it also antagonized histamine-induced bronchospasm in guinea pigs, and published their findings in 1933. Bovet went on to win the 1957 Nobel Prize in Physiology or Medicine for his contribution, and one of their students, Anne-Marie Staub, published the first structure-activity relationship (SAR) study of antihistamines in 1939.
Perathiepin is a neuroleptic drug of the tricyclic family which was developed in the 1960s but was never marketed. In animal studies it was found to possess central depressant, antihistamine, antiserotonergic, and analgesic effects.
Tofenacin is an antidepressant drug with a tricyclic-like structure which was developed and marketed in the United Kingdom and Italy in 1971 and 1981, respectively, by Brocades-Stheeman & Pharmacia. It acts as a serotonin-norepinephrine reuptake inhibitor, and based on its close relation to orphenadrine, may also possess anticholinergic and antihistamine properties. Tofenacin is also the major active metabolite of orphenadrine and likely plays a role in its beneficial effects against depressive symptoms seen in Parkinson's disease patients.
Fenethazine (INN), or phenethazine, is a first-generation antihistamine of the phenothiazine group. Promethazine, and subsequently chlorpromazine, were derived from fenethazine. Fenethazine, in turn, was derived from phenbenzamine.
