S-14671 is a naphthylpiperazine

derivative In mathematics, the derivative of a function of a real variable measures the sensitivity to change of the function value (output value) with respect to a change in its argument (input value). Derivatives are a fundamental tool of calculus. ...

which acts as a 5-HT_1A receptor agonist (pK_i = 9.3) with high efficacy and exceptional ''

in vivo Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, and ...

potency Potency may refer to: * Potency (pharmacology), a measure of the activity of a drug in a biological system * Virility * Cell potency, a measure of the differentiation potential of stem cells * In homeopathic dilutions, potency is a measure of how ...

, and also as a 5-HT_2A and 5-HT_2C receptor antagonist (both are pK_i = 7.8). It displays only low and non-significant

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 Par ...

for 5-HT_1B and 5-HT₃

site Site most often refers to: * Archaeological site * Campsite, a place used for overnight stay in an outdoor area * Construction site * Location, a point or an area on the Earth's surface or elsewhere * Website, a set of related web pages, typical ...

s. In producing 5-HT_1A-mediated effects such as

hypothermia Hypothermia is defined as a body core temperature below in humans. Symptoms depend on the temperature. In mild hypothermia, there is shivering and mental confusion. In moderate hypothermia, shivering stops and confusion increases. In severe ...

and spontaneous tail flicks in rodents, S-14671 is

active Active may refer to: Music * ''Active'' (album), a 1992 album by Casiopea * Active Records, a record label Ships * ''Active'' (ship), several commercial ships by that name * HMS ''Active'', the name of various ships of the British Royal ...

at doses as low as 5 µg

subcutaneously The subcutaneous tissue (), also called the hypodermis, hypoderm (), subcutis, superficial fascia, is the lowermost layer of the integumentary system in vertebrates. The types of cells found in the layer are fibroblasts, adipose cells, and macro ...

, and is about 10-fold more potent than

8-OH-DPAT 8-OH-DPAT is a research chemical of the aminotetralin chemical class which was developed in the 1980s and has been widely used to study the function of the 5-HT1A receptor. It was one of the first major 5-HT1A receptor full agonists to be discove ...

and 100-fold more potent than flesinoxan and

buspirone Buspirone, sold under the brand name Buspar, among others, is a medication primarily used to treat anxiety disorders, particularly generalized anxiety disorder. Benefits support its short-term use. It is taken by mouth, and it may take up to fo ...

. Other 5-HT_1A-mediated effects of S-14671 include induction of flat-body posture,

corticosterone Corticosterone, also known as 17-deoxycortisol and 11β,21-dihydroxyprogesterone, is a 21-carbon steroid hormone of the corticosteroid type produced in the cortex of the adrenal glands. It is of minor importance in humans, except in the very rar ...

secretion, inhibition of

morphine Morphine is a strong opiate that is found naturally in opium, a dark brown resin in poppies (''Papaver somniferum''). It is mainly used as a pain medication, and is also commonly used recreationally, or to make other illicit opioids. T ...

-induced

antinociception An analgesic drug, also called simply an analgesic (American English), analgaesic (British English), pain reliever, or painkiller, is any member of the group of drugs used to achieve relief from pain (that is, analgesia or pain management). It i ...

, and attenuation of the

electrical activity This is a list of electrical phenomena. Electrical phenomena are a somewhat arbitrary division of electromagnetic phenomena. Some examples are: * Biefeld–Brown effect — Thought by the person who coined the name, Thomas Townsend Brown, to ...

of the

dorsal raphe nucleus The dorsal raphe nucleus is located on the midline of the brainstem and is one of the raphe nuclei. It has rostral and caudal subdivisions. * The rostral aspect of the ''dorsal'' raphe is further divided into interfascicular, ventral, ventrolatera ...

. S-14671 has been found to possess powerful efficacy in the rodent

forced swim test The behavioural despair test (or Porsolt forced swimming test) is a test, centered on a rodent's response to the threat of drowning, whose result has been interpreted as measuring susceptibility to negative mood. It is commonly used to measure the ...

and in the pigeon conflict test, indicating marked antidepressant and

anxiolytic An anxiolytic (; also antipanic or antianxiety agent) is a medication or other intervention that reduces anxiety. This effect is in contrast to anxiogenic agents which increase anxiety. Anxiolytic medications are used for the treatment of anxiet ...

effects, respectively, of which are also 5-HT_1A-mediated. It has never been trialed in humans, perhaps due to its potency being too great.

References

{{Piperazines Carboxamides Naphthol ethers Naphthylpiperazines Thiophenes Phenol ethers

See also

References