Drug Abuse Diagnostic Material 01

Introduction of AMP

Ampicillin, Chinese name ampicillin, synonymous with ampicillin, a β-lactam antibiotic, a member of the penicillin family, chemical formula C16H19N3O4S, can treat a variety of bacterial infections.

Ampicillin is a semi-synthetic broad-spectrum penicillin (structure shown above), with broad-spectrum inhibition of Gram-positive, negative, and anaerobic bacteria, and its mechanism of inhibition lies in the following: interfering with the activity of penicillin binding protein (PBP), which is involved in the final step of peptidoglycan synthesis, and which catalyzes the formation of the penta-glycan cross-link between alanine and lysine residues, and this cross-link sustains the cellular activity of the peptide. PBP is involved in the last step of peptidoglycan synthesis and catalyzes the formation of a pentaglycine cross-link between alanine and lysine residues, which maintains the integrity of the cell wall and normal bacterial growth. By inhibiting the synthesis of the bacterial cell wall, the bacteria will be rapidly ruptured and dissolved. Therefore, it can not only inhibit its proliferation, but also kill the bacteria directly. It is sensitive to β-lactamase enzyme, by cleaving the β-lactam ring of ampicillin. This enzyme hydrolyzes β-lactam (β-lactam), a four-membered lactam ring in the structure of ampicillin, rendering it useless. Based on this feature, specially designed plasmids carry the bla gene. Successfully transformed bacteria carry this gene and thus express beta-lactamase and survive in the presence of ampicillin. Clinically, ampicillin is commonly used to treat a variety of bacterial infections and is a very classical antibiotic. Aminobenzylpenicillin is used from time to time in molecular biology experimental research, such as for the preparation of LB medium or LB plates containing ampicillin.

Figure 1 AMP structural formula

Introduction of BAR

Barbituric acid, also known as malonylurea, 2,4,6-pyrimidinetrione, is an organic compound with the chemical formula C4H4N2O3, a white crystalline powder, easily soluble in hot water and dilute acid, soluble in ether, slightly soluble in cold water. The aqueous solution is strongly acidic. It can react with metals to form salts. Barbiturates, derivatives of barbituric acid. Barbituric acid itself has no central inhibitory effect, when the two hydrogen atoms in the C5 position are replaced by the hydrocarbon group to show activity, a series of central inhibitory drugs can be obtained. These drugs produce a sedative-hypnotic effect with varying degrees of central inhibition.

Barbiturates have a generalized depressant effect on the central nervous system. As the dose increases, the central inhibitory effect becomes stronger and weaker, with corresponding sedative, hypnotic, anticonvulsant, antiepileptic and anesthetic effects. Large doses also have inhibitory effects on the cardiovascular system. Overdose can cause paralysis of the respiratory center and death. In non-anesthetic doses acts on gamma-aminobutyric acid (GABAA) A receptor, mainly inhibits polysynaptic responses, attenuates facilitation and enhances inhibition. In the absence of GABA, mimics the effects of GABA by prolonging the opening time of Cl- channels, increasing Cl- permeability, and hyperpolarizing the cell membrane. In addition, barbiturates attenuate or block the excitatory response caused by depolarization of glutamate after its action on the corresponding receptor, causing central inhibition.

Figure 2 BAR structural formula

Introduction of BZO

Benzodiazepines are mostly derivatives of 1,4-benzodiazepines. There are more than 20 types commonly used in clinical practice. Although they are structurally similar, the anxiolytic, sedative-hypnotic, anticonvulsant, muscle relaxant and stabilizing effects of different derivatives are different. Derivatives used for sedation and hypnosis include diazepam (Valium), flurazepam (Fluorazepam), clozapine, oxazepam, and triazolam. This class of drugs are benzodiazepine receptor agonists that cause depression in different parts of the central nervous system.

We focus on the benzodiazepines that play the roles of anxiolytic and sedative-hypnotic, which are its most common uses in psychiatry. To illustrate the pharmacological mechanisms of these two actions, we first introduce a neurotransmitter, gamma amino acid butyric acid (GABA), which is the main inhibitory neurotransmitter in the human body.

GABA receptors can be categorized into three subtypes: GABAA receptors, GABAB receptors, and GABAC receptors.GABAA receptors regulate anxiety and sleep. When benzodiazepines bind to the BZD receptor on the GABAA receptor complex (including GABAergic postsynaptic membrane, GABA receptor, and chloride channel), on the one hand, it opens the chloride channel, and on the other hand, it promotes the binding of GABA to GABAA receptor, so that the frequency of chloride channel opening is increased, which promotes the chloride inward flow from the dual pathway, and enhances central inhibitory effect. In other words, benzodiazepines play an anxiolytic and sedative-hypnotic role by stimulating GABA receptors in the upward reticular activating system, enhancing the inhibition and blockade of cortical and limbic arousal responses after the brainstem reticular structure receives stimulation.

Figure 3 BZO structural formula

Introduction of COC

Cocaine, also known as coca base, is chemically known as phenylmethylbudine. It is used as a local anesthetic or vasoconstrictor. It is mainly used for surface anesthesia due to its good anesthetic effect and strong penetration, but should not be injected due to its high toxicity. It can also be used as a strong natural central stimulant, which also leads to abuse because of its excitatory effect on the central nervous system.

Cocaine damage to the CNS is associated with the dopamine (DA) pathway in the midbrain limbic system. This pathway originates from the ventral tegmental area of the midbrain projecting to the nucleus ambiguus of the ventral striatum and parts of the limbic system, such as the septum, amygdala complex, and pyriform cortex. Whereas the dopamine transporter (DAT) is a membrane protein located in the presynaptic membrane of dopamine neurons, whose main function is to reuptake DA from the synaptic gap, cocaine restricts the duration, extent, and range of action of DA and its receptors by inhibiting DAT on the presynaptic membrane. This in turn realizes the regulatory effect on mental and emotional activities, i.e. the reinforcing effect of cocaine addiction. Under normal physiological conditions, DA and Na+ bind to the corresponding sites on DAT in the presynaptic membrane, followed by Cl- binding to its own site, and finally DAT transports DA from the synaptic gap to intracellular storage. Cocaine and Na+ have the same binding sites on DAT, when cocaine is present, it competes with Na+ to bind to the same site, making DAT unable to bind to DA properly, leading to the accumulation of DA in the synaptic gap, which makes nerve fibers persistently euphoric, and thus giving the user a sense of pleasure.

Figure 4 COC structural formula

Introduction

Cotadutide is a dual agonist of glucagon receptor (GCGR) and glucagon-like peptide-1 receptor (GLP-1R). It has multiple modes of action, not only increasing insulin secretion and decreasing food intake, but also decreasing inflammation and adipogenesis by activating the GLP-1 receptor.

GCGR and GLP-1R are members of the G protein-coupled receptor family, and they are two important "regulators" for maintaining blood glucose homeostasis: GCGR raises blood glucose levels by binding to its ligand, glucagon, during starvation, while GLP-1R functions mainly after food intake by binding to its ligand, glucagon-like peptide-1, and by activating its ligand, glucagon-like peptide-1. By binding to its ligand glucagon-like peptide-1, GLP-1R stimulates insulin secretion, which reduces and maintains postprandial blood glucose at normal levels. Currently, the development of dual agonists targeting GCGR/GLP-1R has become a new direction for the treatment of diabetes, obesity, NASH and other diseases.

of COT 

KMD Bioscience currently has diagnostically active raw materials in the direction of infectious diseases, tumors, inflammation, metabolism, hormones and so on. KMD Bioscience can provide a wide range of bioactive raw materials and technical services for IVD, widely serving domestic and foreign manufacturers of related reagents. These include but are not limited to the custom development of antigens and antibodies, labeling and coupling of antigens and antibodies, antibody pair screening and purification, immunochromatography, enzyme immunoassay and chemiluminescence system optimization and process debugging, and many other technologies.

The inventory of reagents associated with COC and COT that KMD Bioscience can offer: