4-PhPr-3,5-DMA, also known as 4-(3-phenylpropyl)-3,5-dimethoxyamphetamine, is 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 ...
modulator
Signal modulation is the process of varying one or more properties of a periodic waveform in electronics and telecommunication for the purpose of transmitting information.
The process encodes information in form of the modulation or message ...
of the
phenethylamine
Phenethylamine (PEA) is an organic compound, natural monoamine alkaloid, and trace amine, which acts as a central nervous system stimulant in humans. In the brain, phenethylamine regulates monoamine neurotransmission by binding to trace ami ...
and
amphetamine
Amphetamine (contracted from Alpha and beta carbon, alpha-methylphenethylamine, methylphenethylamine) is a central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, an ...
methoxy group
In organic chemistry, a methoxy group is the functional group consisting of a methyl group bound to oxygen. This alkoxy group has the formula .
On a benzene ring, the Hammett equation classifies a methoxy substituent at the ''para'' position a ...
s in the 3 position instead of 2 position on the phenyl ring and has a bulky substitution at the 4 position of the phenyl ring.
The affinities (Ki) of 4-PhPr-3,5-DMA 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, ...
selectivity
Selectivity may refer to:
Psychology and behaviour
* Choice, making a selection among options
* Discrimination, the ability to recognize differences
* Socioemotional selectivity theory, in social psychology
Engineering
* Selectivity (radio), a ...
for the serotonin 5-HT2A receptor over the serotonin 5-HT2C receptor. Its affinities for the serotonin 5-HT2A and 5-HT2C receptors in the study were approximately 8-fold and 1.6-fold higher than those of
DOB
DOB or Dob often refers to date of birth.
DOB or Dob may also refer to:
Biochemistry
* 2,5-dimethoxy-4-bromoamphetamine, Bromo-DMA, a psychedelic drug
** Meta-DOB, related substance
** Methyl-DOB, related substance
* HLA-DOB, human gene
Organiz ...
, respectively. The drug was a
full agonist
An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the agoni ...
of the serotonin 5-HT2A receptor in terms of
phosphatidylinositol
Phosphatidylinositol or inositol phospholipid is a biomolecule. It was initially called "inosite" when it was discovered by Léon Maquenne and Johann Joseph von Scherer in the late 19th century. It was discovered in bacteria but later also found ...
(PI)
hydrolysis
Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution reaction, substitution, elimination reaction, elimination, and solvation reactions in which water ...
( = 109% relative to serotonin). However, in the presence of the serotonin 5-HT2A receptor
silent antagonist
A receptor antagonist is a type of receptor ligand or drug that blocks or dampens a biological response by binding to and blocking a receptor rather than activating it like an agonist. Antagonist drugs interfere in the natural operation of recep ...
ketanserin
Ketanserin, sold under the brand name Sufrexal, is an antihypertensive agent which is used to treat arterial hypertension and vasospasm, vasospastic disorders. It is also used in scientific research as an antiserotonergic medication, agent in th ...
, which should have abolished stimulation, 4-PhPr-3,5-DMA still produced 43% activation of PI hydrolysis. These findings suggest that 4-PhPr-3,5-DMA may be acting in the
assay
An assay is an investigative (analytic) procedure in laboratory medicine, mining, pharmacology, environmental biology and molecular biology for qualitatively assessing or quantitatively measuring the presence, amount, or functional activity ...
via a combination of both serotonin 5-HT2A receptor partial agonism and another unknown ketanserin-insensitive
mechanism
Mechanism may refer to:
*Mechanism (economics), a set of rules for a game designed to achieve a certain outcome
**Mechanism design, the study of such mechanisms
*Mechanism (engineering), rigid bodies connected by joints in order to accomplish a ...
.
The observed serotonin 5-HT2A receptor agonist activity of 4-PhPr-3,5-DMA was surprising, as previously studied DOx
derivative
In mathematics, the derivative is a fundamental tool that quantifies the sensitivity to change of a function's output with respect to its input. The derivative of a function of a single variable at a chosen input value, when it exists, is t ...
s with bulky 4-position substituents such as DOHx had consistently acted as
antagonist
An antagonist is a character in a story who is presented as the main enemy or rival of the protagonist and is often depicted as a villain. In addition, the 3,5-dimethoxy substitution pattern being optimal in the study was unexpected, as the 2,5-dimethoxy pattern has been found to be optimal in the DOx drugs. The study's findings suggest that bulky substitutions at the 4 position of DOx-like amphetamines can provide enhanced serotonin 5-HT2A receptor affinity but will not inevitably result in antagonism. Instead, agonism, and possible psychedelic effects, may be retainable with specific substitution patterns.
An analogue is 4-PhPr-2,5-DMA, which is also a weak
partial agonist
In pharmacology, partial agonists are drugs that bind to and activate a given Receptor (biochemistry), receptor, but have only partial Intrinsic activity, efficacy at the receptor relative to a full agonist. They may also be considered Ligand (bio ...
3C-BZ
3C-BZ, also known as 4-benzyloxy-3,5-dimethoxyamphetamine or as 3C-benzscaline, is a lesser-known psychedelic drug and a substituted amphetamine. 3C-BZ was first synthesized by Alexander Shulgin.
Use and effects
In Shulgin's book ''PiHKAL'', the ...
*
Benzscaline
Benzscaline (BZ), also known as 4-benzyloxy-3,5-dimethoxyphenethylamine (4-BzlO-3,5-DMPEA), is a serotonin receptor agonist and possible serotonergic psychedelic of the phenethylamine and scaline families.
It is a potent serotonin 5-HT2A rece ...