Milipertine (, ; developmental code name WIN-18935) is a

drug A drug is any chemical substance other than a nutrient or an essential dietary ingredient, which, when administered to a living organism, produces a biological effect. Consumption of drugs can be via insufflation (medicine), inhalation, drug i ...

of the

pertine The pertines are a group of antipsychotics of the cyclized tryptamine and phenylpiperazine families that includes the following drugs: * Alpertine (WIN-31665) * Milipertine (WIN-18935) * Oxypertine (WIN-18501) * Solypertine (WIN-18413) Oxype ...

group described as an

antipsychotic Antipsychotics, previously known as neuroleptics and major tranquilizers, are a class of Psychiatric medication, psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), p ...

neuroleptic Antipsychotics, previously known as neuroleptics and major tranquilizers, are a class of psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizoph ...

, and

tranquilizer A sedative or tranquilliser is a substance that induces sedation by reducing irritability or excitement. They are central nervous system (CNS) depressants and interact with brain activity, causing its deceleration. Various kinds of sedatives c ...

which was under development for the treatment of

schizophrenia Schizophrenia () is a mental disorder characterized variously by hallucinations (typically, Auditory hallucination#Schizophrenia, hearing voices), delusions, thought disorder, disorganized thinking and behavior, and Reduced affect display, f ...

but was never marketed.

Structurally A structure is an arrangement and organization of interrelated elements in a material object or system, or the object or system so organized. Material structures include man-made objects such as buildings and machines and natural objects such as ...

, it is a

substituted tryptamine Substituted tryptamines, or simply tryptamines, also known as serotonin analogues (i.e., 5-hydroxytryptamine analogues), are organic compounds which may be thought of as being derived from tryptamine itself. The molecular structures of all trypt ...

and a piperazinylethylindole. The drug is closely structurally related to other "pertines" including

alpertine Alpertine (, ; developmental code name WIN-31665) is a drug of the pertine group described as an antipsychotic, neuroleptic, and tranqulizer which was never marketed. Structurally, it is a substituted tryptamine and a piperazinylethylindole. T ...

oxypertine Oxypertine, sold under the brand name Oxypertine among others, is an antipsychotic medication of the pertine group which was previously used in the treatment of schizophrenia but is no longer marketed. It was also evaluated for the treatment of ...

, and

solypertine Solypertine (; developmental code name WIN-18413), also known as solypertine tartrate () in the case of the tartrate salt, is a drug of the pertine group described as an antiadrenergic (or adrenolytic/sympatholytic) and as also potentially posse ...

, which are also tryptamines and piperazinylethylindoles. The related drug oxypertine shows high

affinity Affinity may refer to: Commerce, finance and law * Affinity (law), kinship by marriage * Affinity analysis, a market research and business management technique * Affinity Credit Union, a Saskatchewan-based credit union * Affinity Equity Pa ...

for the

serotonin Serotonin (), also known as 5-hydroxytryptamine (5-HT), is a monoamine neurotransmitter with a wide range of functions in both the central nervous system (CNS) and also peripheral tissues. It is involved in mood, cognition, reward, learning, ...

5-HT₂ and

dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. It is an amine synthesized ...

D₂ receptors (K_i = 8.6nM and 30nM, respectively) and is also known to act as a catecholamine depleting agent. Oxypertine, milipertine, and solypertine all antagonize the behavioral effects of

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 ...

, a

serotonin receptor 5-HT receptors, 5-hydroxytryptamine receptors, or serotonin receptors, are a group of G protein-coupled receptor and ligand-gated ion channels found in multiple tissues including the central and peripheral nervous systems. They mediate both ex ...

agonist An agonist is a chemical that activates a Receptor (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an R ...

, and

apomorphine Apomorphine, sold under the brand name Apokyn among others, is a type of aporphine having activity as a non- selective dopamine agonist which activates both D2-like and, to a much lesser extent, D1-like receptors. It also acts as an antago ...

, a

dopamine receptor Dopamine receptors are a class of G protein-coupled receptors that are prominent in the vertebrate central nervous system (CNS). Dopamine receptors activate different effectors through not only G-protein coupling, but also signaling through diff ...

, in animals. ''ortho''-Methoxyphenylpiperazine (oMeOPP) has been said to be a

metabolite In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...

of milipertine, as well as of oxypertine and several other drugs. Milipertine produced troublesome

side effect In medicine, a side effect is an effect of the use of a medicinal drug or other treatment, usually adverse but sometimes beneficial, that is unintended. Herbal and traditional medicines also have side effects. A drug or procedure usually use ...

s in

clinical studies Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, dietar ...

including

orthostatic hypotension Orthostatic hypotension, also known as postural hypotension, is a medical condition wherein a person's blood pressure drops when they are standing up ( orthostasis) or sitting down. Primary orthostatic hypotension is also often referred to as ne ...

drowsiness Somnolence (alternatively sleepiness or drowsiness) is a state of strong desire for sleep, or sleeping for unusually long periods (compare hypersomnia). It has distinct meanings and causes. It can refer to the usual state preceding falling asleep ...

extrapyramidal symptoms Extrapyramidal symptoms (EPS) are signs and symptoms, symptoms that are wikt:archetypical, archetypically associated with the extrapyramidal system of the brain's cerebral cortex. When such symptoms are caused by medications or other drugs, they ...

elevated liver enzymes In medicine Medicine is the science and Praxis (process), practice of caring for patients, managing the Medical diagnosis, diagnosis, prognosis, Preventive medicine, prevention, therapy, treatment, Palliative care, palliation of their injur ...

, and

weight loss Weight loss, in the context of medicine, health, or physical fitness, refers to a reduction of the total body mass, by a mean loss of fluid, body fat (adipose tissue), or lean mass (namely bone mineral deposits, muscle, tendon, and other conn ...

. The side effects of milipertine occurred too frequently and at doses well below those producing antipsychotic effects and its development was abandoned. Milipertine 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 1968.

References

{{Tryptamines Abandoned drugs 2-Alkyltryptamines Antipsychotics Pertines Phenylpiperazines

See also

References