PEPAP
Encyclopedia
PEPAP is an opioid
analgesic
that is an analog
of pethidine
(meperidine).
It is related to the drug MPPP
, with an N-phenethyl group in place of the N-methyl substitution and an acetate
ester rather than propionate
. PEPAP is approximately 6-7 times more potent than morphine in laboratory rats. PEPAP presumably has similar effects to other opioids, producing analgesia, sedation and euphoria. Side effects can include itching, nausea
and potentially serious respiratory depression which can be life-threatening.
PEPAP has been found to be a potent CYP2D6
inhibitor, which makes it likely to cause adverse interactions with some other drugs, although the inhibitory potency of PEPAP is less than that of MPPP. (Both cocaine and methadone are also CYP2D6
inhibitors and could, in theory, potentiate the effect.)
It is unlikely that the tetrahydropyridine byproducts that may be formed during the synthesis of PEPAP are neurotoxic in the same way as the MPPP byproduct MPTP
. It appears that the N-methyl group of MPTP is required for neurotoxic activity. In animal experiments, only MPTP analogues that preserved the N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine structure were active as dopaminergic neurotoxins. Most structural changes, including replacing the N-methyl group with other substituents, abolished neurotoxicity.
There is evidence that the clandestine manufacturers who produced MPPP in the 1970s (included the tainted batch) went on to produce PEPAP in an attempt to avoid using watched precursors or drug intermediates that were illegal.
Opioid
An opioid is a psychoactive chemical that works by binding to opioid receptors, which are found principally in the central and peripheral nervous system and the gastrointestinal tract...
analgesic
Analgesic
An analgesic is any member of the group of drugs used to relieve pain . The word analgesic derives from Greek an- and algos ....
that is an analog
Analog (chemistry)
In chemistry, a structural analog , also known as chemical analog or simply analog, is a compound having a structure similar to that of another one, but differing from it in respect of a certain component. It can differ in one or more atoms, functional groups, or substructures, which are replaced...
of pethidine
Pethidine
Pethidine or meperidine Pethidine (INN) or meperidine (USAN) Pethidine (INN) or meperidine (USAN) (commonly referred to as Demerol but also referred to as: isonipecaine; lidol; pethanol; piridosal; Algil; Alodan; Centralgin; Dispadol; Dolantin; Mialgin (in Indonesia); Petidin Dolargan (in Poland);...
(meperidine).
It is related to the drug MPPP
MPPP
1-Methyl-4-phenyl-4-propionoxypiperidine or Desmethylprodine is an opioid analgesic drug developed in the 1940s by researchers at Hoffmann-La Roche. It is not used in clinical practice, but has been illegally manufactured for recreational drug use...
, with an N-phenethyl group in place of the N-methyl substitution and an acetate
Acetate
An acetate is a derivative of acetic acid. This term includes salts and esters, as well as the anion found in solution. Most of the approximately 5 billion kilograms of acetic acid produced annually in industry are used in the production of acetates, which usually take the form of polymers. In...
ester rather than propionate
Propionate
The propanoate or propionate ion is C2H5COO− .A propanoic or propionic compound is a salt or ester of propanoic acid....
. PEPAP is approximately 6-7 times more potent than morphine in laboratory rats. PEPAP presumably has similar effects to other opioids, producing analgesia, sedation and euphoria. Side effects can include itching, nausea
Nausea
Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...
and potentially serious respiratory depression which can be life-threatening.
PEPAP has been found to be a potent CYP2D6
CYP2D6
Cytochrome P450 2D6 , a member of the cytochrome P450 mixed-function oxidase system, is one of the most important enzymes involved in the metabolism of xenobiotics in the body. Also, many substances are bioactivated by CYP2D6 to form their active compounds...
inhibitor, which makes it likely to cause adverse interactions with some other drugs, although the inhibitory potency of PEPAP is less than that of MPPP. (Both cocaine and methadone are also CYP2D6
CYP2D6
Cytochrome P450 2D6 , a member of the cytochrome P450 mixed-function oxidase system, is one of the most important enzymes involved in the metabolism of xenobiotics in the body. Also, many substances are bioactivated by CYP2D6 to form their active compounds...
inhibitors and could, in theory, potentiate the effect.)
It is unlikely that the tetrahydropyridine byproducts that may be formed during the synthesis of PEPAP are neurotoxic in the same way as the MPPP byproduct MPTP
MPTP
MPTP is a neurotoxin precursor to MPP+, which causes permanent symptoms of Parkinson's disease by destroying dopaminergic neurons in the substantia nigra of the brain...
. It appears that the N-methyl group of MPTP is required for neurotoxic activity. In animal experiments, only MPTP analogues that preserved the N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine structure were active as dopaminergic neurotoxins. Most structural changes, including replacing the N-methyl group with other substituents, abolished neurotoxicity.
There is evidence that the clandestine manufacturers who produced MPPP in the 1970s (included the tainted batch) went on to produce PEPAP in an attempt to avoid using watched precursors or drug intermediates that were illegal.