OXY/PCP/PPX/TcAs

OXY Introduction

Oxycodone (OXY), with the molecular formula C18H21NO4, is a semi-synthetic derivative of Tibaine. Oxycodone is a semi-synthetic pure opioid receptor agonist with a mechanism of action similar to that of morphine, acting mainly through agonism of opioid receptors in the central nervous system, with moderate analgesic potency.

As with all other pure opioid agonists, oxycodone's analgesic effect increases with increasing dose. The exact mechanism of oxycodone's analgesic effect is not known. Specific CNS opioid receptors with endogenous opioid-like properties have been identified in the brain and spinal cord and may be involved in the analgesic effects of oxycodone. Oxycodone produces respiratory depression by direct action on brainstem respiratory centers, including decreased responsiveness to carbon dioxide and electrical stimulation. Oxycodone inhibits the cough reflex by direct action on the cough center. Cough suppressant effects may be produced at doses lower than conventional analgesic doses. Oxycodone may cause pupil dilation, even in complete darkness. In the case of oxycodone overdose there may be marked pupil dilation rather than pupil reduction.

Figure 1 The structural formula of OXY

Introduction to PCP

Phencyclidine (PCP) affects the brain's neurotransmitter system by inhibiting the reuptake processes of dopamine, norepinephrine, and 5-hydroxytryptamine, and also inhibits the function of glutamate by blocking NMDA receptors. These receptors are responsible for the regulation of pain sensation, emotion, learning and memory functions, etc. PCP inhibits the function of these receptors and deprives the brain of normal sensory experience, i.e., detachment from reality. However, high doses of phenylcyclohexylpiperidine can also activate these receptors.The effects of PCP on the population depend on the dose of PCP and the route of administration.

Glutamatergic effects: γ-aminobutyric acid (GABA) is an inhibitory neurotransmitter, on the contrary, glutamate is an excitatory neurotransmitter.There are three types of glutamate receptors that promote ion flow: α-amino-3-hydroxy-5-methyl-4-isoxazolylpropionic acid (AMPA) receptors, erythrocyanine receptors, and N-methyl-D-aspartic acid (NMDA) receptors.All of them cause excitatory intoxication. Ca2+ enters into the cell, activates phospholipase C, destroying cytoskeletal membrane components; activates nucleic acid endonuclease, destroying DNA, leading to cellular dysfunction, and ultimately leading to cell death. Glutamatergic hyperactivity can cause affective disorders, anxiety disorders, movement disorders, substance dependence and anorexia, glutamatergic insufficiency can cause schizophrenia and episodic somnolence, and glutamatergic hyperactivity or hypoglutamatergic hypoglutamatergic hypoglutamatergic hypoglutamate can cause cognitive impairment.

Glutamatergic function is reduced in the cerebrospinal fluid, and the reduction in glutamatergic activity is due to decreased levels of the glutamate receptor, N-methyl-d-menthane (NMDA) receptor. In addition the noncompetitive NMDA receptor antagonist phencyclidine, phencyclidine (PCP), causes positive symptoms, negative symptoms, and symptoms of cognitive impairment in both normal populations and schizophrenic patients. Antipsychotic drugs can block some of the clinical effects of phencyclidine (PCP), so they can ameliorate positive symptoms, negative symptoms and cognitive impairment.

Figure 2 Structural formula of PCP

Introduction of PPX

Propoxyphene is structurally similar to methadone and its metabolites with a half-life of 8-24 hours. Since 2010, the FDA has recommended avoiding propoxyphene because of its cardiotoxic effects, even at therapeutic doses. Propoxyphene is usually detected in the urine as part of a drug abuse test.

Propoxyphene is a synthetic opioid with a structure recognizable to methadone, dextropropoxyphene (dextropropoxyphene) is a noncompetitive NMDA antagonist, and overdose of propoxyphene can result in serious side effects including convulsions, cardiac arrhythmias, and cardiac block, and its active metabolite, desmethylpropoxyphene ( Its active metabolite, norpropoxyphene, has weak opioid activity and can cause convulsions, and in 2005 British authorities announced the gradual withdrawal of this drug from the market. Propoxyphene is metabolized in the liver and excreted in the urine as norpropoxyphene. Therefore, the presence of propoxyphene or its metabolites in the urine is indicative of propoxyphene use.

Figure 3 PPX structural formula

Introduction to TCA

Tricyclic antidepressants (TcAs) are one of the most commonly used drugs for the clinical treatment of depression, with a core structure consisting of a seven-membered heterocyclic ring in the middle with a benzene ring attached on both sides. Promethazine was the first compound found to have antidepressant effects.TCAs are mainly metabolized in the liver, and the metabolizing enzymes involved are CYP1A2, CYP2D6, CYP3A4, etc. The main metabolism is tricyclic nuclear oxidation. The main metabolism is tricyclic nuclear oxidation, such as hydroxylation of carbon atoms at position 2 or 10 (catalyzed by CYP2D6), oxidation of fatty side chains, and demethylation of nitrogen atoms (catalyzed by CYP3A4). They are all non-selective monoamine uptake inhibitors, which mainly inhibit the reuptake of norepinephrine (NA) and 5-hydroxytryptamine (5-HT), increase the concentration of these two excitatory neurotransmitters in the synaptic gap, and promote the function of transmission between synapses to become aroused, which effectively alleviates depression.

TCAs block the reuptake of NA and 5-HT by norepinephrine (NA)-ergic and 5-hydroxytryptamine (5-HT)-ergic nerve endings, increasing the concentration of synaptic interstitial monoamine transmitters, which clinically manifests itself as an improvement in depressive symptoms. The current study found that the inhibitory effect of antidepressants on transmitter reuptake occurs immediately, while long-term use of the drug can reduce the sensitivity of the receptor (down-regulation), which is closely related to the lag in the clinical effect of antidepressants (the effect of the drug takes effect after 2-3 weeks).The blockade of NA reuptake increases the concentration of endogenous NA in synaptic space, which in turn can reduce the sensitivity of the α2 receptor in the presynaptic membrane, and long-term use of the drug may also reduce the central α2 receptor. The inhibition of 5-HT reuptake also increases the endogenous 5-HT concentration in the synaptic gap at the cytosolic site, which ultimately leads to an antidepressant effect by down-regulating 5-HT1A receptors in the presynaptic cytosolic membrane and increasing the release of 5-HT from the terminals.TCAs also have a strong effect on blocking 5-HT2A receptors.

Figure 4 Structural formula of promethazine

KMD Bioscience's products cover almost the whole field of immunodiagnosis, mainly used in myocardial, tumor, autoimmune diseases, thyroid gonadal, infectious diseases, eugenics, etc. Meanwhile, KMD Bioscience can provide quality control serums and dehormone serums to support its products. KMD Bioscience's antibody diagnostic raw materials and antigen diagnostic raw materials are strictly monitored during the R&D and production stages, and the performance indexes (specificity, activity, stability, etc.) of the antibodies/antigens are analyzed, and the reagents of international manufacturers are used for comparison, so as to ensure that IVD raw materials have the characteristics of small batch-to-batch/intra-batch variations, wide linear ranges, good stability, high sensitivity, and so on.

The inventory of reagents associated with OXY、PCP and TCA that KMD Bioscience can offer: