Receptor

A receptor is a component of cell membranes that interacts and binds to a drug to initiate biochemical events leading to the drugs observed effects or to inhibit any specific physiological action in the body.

Drugs that bind to the receptor and initiates biological reactions in the body are known are agonist. On the other hand, drugs that inhibit the action of an agonist is known as antagonist. 

Nowadays, structural information of many receptor proteins are gained that has led to the developed molecular processes in drug-receptor interactions. 

A numerous numbers of receptor protiens have been discovered and their isolation, purification, cloning and sequence of amino acids has been established. Most of the receptors are protein in nature and some are glycoproteins. 

However, the signal transport process and mechanism of action of receptors are governed by a limited number of basic mechanisms. There are four super families of receptor proteins that covers most of the receptor proteins. The four super families are:

1. Ligand-gated ion channels

2. G-protein coupled receptors 

3. Intracellular receptors 

4. Tyrosine kinase linked receptors

Ligand-gated ion channels (ionotropic receptors)

These are membrane bound receptors that are directly linked to an ion channel. These are large multisubunit receptors containing 4-5 subunits. When open, they allows the passage of Na+,K+,Ca++,Cl–.

Ligand gated ion channels are classified into three families based on their molecular and protein structure criteria. 

01. "cys-loop" ligand gated ion channels 

E.g: 5-HT3,GABA-A,GABA-B receptors

02. Glutamate receptors 

E.g: kinate receptors, metabotropic receptors, NMDA receptors

03. ATP-sensitive P2X receptors.

Their function include mediating neurotransmitter responses to the central and peripheral nervous system, also maybe in non-excitable cells. However, ligand itself is not the substance that is transmitted into the cell. They function by facilitating the signal transmission in CNS or PNS. 

Example of Ligand-gated ion channel receptor drugs include: Acetylcohline, Histamine, Serotonin.

G-protein(Guanine nucleotide-rugulatory protein)  coupled receptors

These are membrane-bound receptors coupled to G-proteins. After the activation of G-proteins, a variety of biochemical signal transmission pathways may be activated. These are also known as metabotropic receptors.

In eukaryotes, G-protein coupled receptors are the most variable and largest group of membrane receptors. Researchers claimed that about one half of the marketed drugs acts by binding with GPCRs.

Functional mechanism include the following pathway 

Receptor binding :

 Agonist 

Agonists are types of drug that bind and activate a receptor and induces many physiological reactions. They can make physiological responses in the body and turn the neurotransmitters in action.

Agonists type with examples 

01. Full agonist 

E.g: heroin, methadone, morphine, opium

02. Partial agonist

E.g: buspirone, buprenorphine, narclozapine

03. Orthosteric agonist

E.g: imatinib

04. Direct agonist

E.g: morphine, nicotine 

05. Indirect agonist

E.g: cocaine 

06. Inverse agonist

E.g: GABAA, mu opoid, histamine

07. Physiological agonist

E.g: epinephrine & hepatocyte growth factor(HGF)

08. Endogenous agonist

E.g: serotonin for serotonin receptors & dopamine for dopamine receptors

09. Exogenous agonist

E.g: heroin, caffeine, ibuprofen 

10. Selective agonist

E.g: buspirone is a selective agonist for serotonin 5-HT1A. 

Antagonist 

Antagonists are the type of drug that limits/ inhibits the action of agonists. They exert their pharmacological effects by playing the opposing role of the agonists. They works by blocking the activation of certain receptors of cell and by preventing biological responses.

Types of Antagonists with example 

1. Full antagonist 

E.g: naltrexone & naloxone

2. Chemical antagonist 

E.g: narcan, naltrexone

3. Physiological antagonist 

E.g: glucagon

4. Pharmacokinetic antagonist 

E.g: phenobarbital 

5. Allosteric antagonist 

E.g: barbiturates & benzodiazepines

6. Negative allosteric antagonist 

E.g: flumazenil, bicuculline, gabazine

7. Competitive antagonist 

E.g: naloxone

8. Non-competitive antagonist 

E.g: ketamine

9. Partial antagonist 

E.g: adrenargic blockers

10. Mixed antagonist 

E.g: pentazocine, butorphanol, buprenorphine

General Mechanism of Action of Agonist