1. Home
  2. >
  3. Blog
  4. >

15 important GPCR binding drugs in pharmacology

by egpat         12-12-2017

Drugs can bind to the various protein targets among which G-protein coupled receptors (GPCR) hold their flagship.

It is not surprising that many of clinically important drugs today act either on GPCR or on enzymes. The list of GPCR binding drugs is increasing slowly gaining the more importance of future research focussed on these targets.

It’s great. Do we have well established drugs targeting GPCR right now?

Yes, of course. A lot of drugs bind to these targets and here we will see the list of all such drugs along with examples.

First of let’s see what is GPCR?

It is simply a surface receptor expressed on the membrane which carries the chemical signal across the membrane into the cell on binding of ligand to the receptor.

So its role is to bring the communication between extracellular environment with intracellular environment.

It carries the chemical signal and converts it in to chain of cellular actions which bring the proposed cellular specific t each ligand and its receptor.

For example, epinephrine binds to the β2 receptor on bronchial muscle which then activates adenylyl cyclase system releasing cAMP. The later can cause phosphorylation of myosin light chain kinases (MLCK) leading to relaxation of bronchial muscle.

what are the drugs that bind to GPCR

Okay, before going to discuss the list of GPCR binding drugs, let’s see which type of drugs are not included in this list.

Drugs that don’t bind to GPCR

First, we can exclude the drugs that directly act on ion channels which mostly block the ion channel preventing its opening.

Drugs like voltage gated sodium channel blockers, calcium channel blockers and potassium channel blockers all act directly act on ion channels and hence not come under the list.

Examples include lidocaine, quinidine, phenytoin, verapamil, diltiazem, nifedipine and amiodarone.

It’s fine. So drugs acting on ion channels are excluded. Then, can we include all drugs acting on receptors into the list?

Certainly, ‘no’, we can’t.

Few of the drugs act on receptor coupled with ion channels again not fall into the list.

These receptors, commonly called as ionotropic receptors, are not GPCR hence all drugs acting on these should be properly differentiated.

For instance, non-depolarising neuromuscular blockers like d-tubocurarine, pancuronium, vecuronium, atracurium and depolarising neuromuscular blocker like suxamethonium all act on nicotinic acetylcholine receptors (nAChR) which are of ionotropic receptors.

Next to remember is about hormones.

Most of the steroidal hormones act on nuclear receptors located within the cell again does not fit into the list.

What about insulin?

Yes, it’s too outside this list as it acts on kinase linked receptors.

It’s nice, anything else?

Again a large list of drugs act on enzymes is an exception to the GPCR binding drugs.

ACE inhibitors, MAO inhibitors, acetylcholinesterase inhibitors, NSAIDs, carbonic anhydrase inhibitors and many chemotherapeutic drugs like penicillins, all act on enzymes as drug targets.

Finally loop diuretics, thiazide diuretics and proton pump inhibitors act on transporters are also exclusions.

Now you may think that the exclusion list is very large, so what the role of GPCR binding drugs in therapy?

But you may still see a large list of drugs acting on GPCR and more interestingly all these drugs are therapeutically highly significant.

So, let’s explore how various classes of drugs bind to GPCR.

Drugs that bind to GPCR

Many of the chemical mediators and neurotransmitters bind to GPCR producing their physiological response.

Similar is the case with many drugs acting on these receptors.

So let’s list out all the drugs that bind to GPCR.

Cholinergic agonists

All muscarinic acetylcholine receptors are G-protein coupled receptors present at various locations such as CNS, heart, many smooth muscles and exocrine glands.

Cholinergic agonist like carbachol, bethanechol and pilocarpine bind to GPCR and produce their pharmacological actions.

Carbachol and pilocarpine are two of the drugs indicated for treatment of glaucoma.

Similarly bethanechol binds to GPCR at GI smooth muscle and bladder resulting in their contraction. Theat’s why this drug can be indicated for hyptotonic conditions or postoperative conditions like megacolon where GI motility is reduced.


Just like muscarinic agonists, anticholinergics act as examples for drugs bind to GPCR.

We have lot of drugs in this category used for various clinical purpose and important drugs include

  • Atropine
  • Scopolamine
  • Dicyclomine
  • Ipratropium
  • Tiotropium
  • Cyclopentolate
  • Tropicamide
  • Darifenacin
  • Tolterodine
  • Oxybutynin

Atropine is one the drug in this category used for multiple clinical conditions such as mydriatic, pre-anaesthetic, antispasmodic and as antidote for physostigmine poisoning.

α1 agonist

What will you do if your nostrils are blocked? Yes, get a nasal spray just to relieve this block within few minutes.

What is the drug in that?

These are the nasal decongestant mainly have any of these drugs

  • Oxymetazoline
  • Xylometazoline

Yes, again these drugs bind to GPCR, particularly act on α1 receptors which produce nasal vasoconstriction and relieve from congestion

Note: Nasal congestion is due to nasal vasodilatation which increases capillary permeability resulting in swelling and obstruction of nasal pathways. In order to relieve form this congestion the nasal blood vessels should be constricted.

So, simply these drugs act as vasoconstrictors act locally at nasal blood vessels.

But what happens, if they are internally consumed?

Yes, this is of important thing to consider. These drugs can increase blood pressure if they are consumed internally. That’s why they are restricted for external purpose only.

Note: Few of the nasal sprays don’t contain any medicament instead they have normal saline solution. Interestingly, saline solution can restore the nasal congestion in mild conditions and it is not associated with any risk of hypertension even consumed internally.

α2 agonist

Have you though anytime an agonist can produce antagonistic effects to the neurotransmitter?

Yes, that can be found with clonidine.

Clonidine again binds to GPCR, this time at α2 adrenergic receptors which are present at presynaptic nerve terminals and decrease release of norepinephrine.

So clonidine binds to GPCR at central level thereby inhibits central sympathetic discharge decreasing blood pressure.

Hence it is indicated as centrally acting antihypertensive. At the same time it can also be used in treatment of drug addiction in the narcotic patients.

β1 agonist

What happens if heart is not working? The entire systemic circulation is reduced and every process in the body will collapse.

Is there any drug in such conditions?

Yes, we can have cardiac stimulants which are used at emergency or shock conditions where heart is not responding and functioning significantly.

Dobutamine is such a drug that acts as β1 agonist and binds to GPCR to increase both rate and force of contraction of the heart.

So, it is one of the drugs that indicated in congestive heart failure and cardiogenic shock.

β2 agonists

Now these drugs act on bronchioles.

Drugs like albuterol, terbutaline, salmeterol and formoterol all act as bronchodilators hgihy useful in respiratory disorders like asthma and chronic obstructive pulmonary disorder (COPD).

These drugs bind to GPCR at β2 receptors thereby increase cAMP levels in smooth muscle resulting in relaxation.

Alpha blockers

Just like agonist, alpha antagonists (commonly called as alpha blockers) bind to GPCR but to produce antagonistic effect.

Drugs like phenoxybenzamine and phentolamine are two non-selective alpha blockers that can be indicated during surgical removal of adrenal tumor, phaeomchomocytoma.

On the other hand, drugs like prazosin, doxazosin and terazosin are selective α1 blockers that bind to GPCR specifically to produce vasodilatation.

Are they acting as drug of choice for hypertension?

No, even though they produce vasodilatation and reduce blood pressure, the same effect is responsible for orthostatic hypotension and reflex tachycardia.

So the patients taking these drugs may have sudden falling on standing and a feeling of dizziness. Even these drugs can also produce tachycardia by reflex mechanism.

Beta blockers

This is a widely used category all the drugs ending with a common suffix “-olol”.

These drugs bind to GPCR selectively or non-selectively at beta adrenergic receptors.

Non-selective beta blockers include propranolol, timolol, pindolol and nadolol.

Similarly selective beta blockers include atenolol, metorprolol, esmolol, acebutolol, carterolol and betaxolol.

Beta blockers have wide clinical indications such as antihypertensives, antianginals, antiarrhythmics and anxiolytics.


You know histamine is one of the important mediators for allergic reactions.

How it acts?

Again it binds to GPCR and increases cAMP producing allergic and inflammatory response.

So, antihistamines also bind to GPCR at H1 receptors and antagonise the functions of histamine.

We have two generations of antihistamines, the old generation being sedative in nature due to their permeability into the CNS.

Few of these drugs include diphenhydramine, doxylamine, cyclizine, meclizine, promethazine and chlorpheniramine.

On the other hand, new generation antihistamines also bind to GPCR but more peripherally and hence less sedative in nature. These drugs include cetrizine, levocetrizine, loratidine, desloratidine, and fexofenadine

H2 antagonists

Like H1 antagonists, H2 antagonists also bind to HPCR at gastric parietal cells and thereby decrease histamine-induced gastric acid secretion.

Drug such as cimetidine, ranitidine, nizatidine and famotidine all bind to GPCR and used as anti-ulcer agents.

Among these drugs, cimetidine not only binds to GPCR but also binds to steroid receptors resulting in gynaecomastia.


Buspirone is one of the anxiolytic that binds to GPCR at 5-HT1A receptors. It has few advantages over benzodiazepines such as lack of motor incordination and memory problems.

But it is not immediately acting and it takes few weeks after the treatment for showing its beneficial effects against anxiety.


Few of the drugs like promethazine and haloperidol bind to GPCR of dopamine receptors and decrease emesis.

Similarly other drugs like domperidone and metoclopramide bind to GPCR at 5-HT4 receptors as well as some action on dopamine receptors and increase GI motility again producing antiemetic effect.

Antimigraine agents

Well known triptan drugs also bind to GPCR acting as 5-HT1D agonists. These drugs produce cerebral vasoconstriction thereby decrease headache in migraine.

As with cerebral vasoconstriction, they can also produce coronary vasoconstriction which is of important concern precipitating angina and other cardiovascular problems.


Antipsychotics mainly bind to GPCR at dopaminergic neurons reducing their hyperfunctionality particularly at limbic and cortex.

Old generation drugs like chlorpromazine, fluphenazine, haloperidol, thiothixene bind to GPCR at mesolimbic, mesocortical and nigrostriatal pathways. These drugs are associated with motor side effects commonly called as extrapyramidal side effects (EPS).

On the other hand, new generation antipsychotics like risperidone, quetiapine, aripiprazole, olanzapine all bind to GPCR at D2, D1 and 5-HT2A producing less extrpyramidal side effects.


How we control pain with drugs?

The best part is with Non-steroidal anti-inflammatory agents(NSAIDs) with lot of drugs in the category, most of them being OTC drugs.

But what is about severe and chronic pain?

Yes, here opioids come into the picture.

These are the potent analgesics that act both centrally and peripherally to produce analgesia and highly useful in management of moderate to severe pain conditions.

These drugs bind to GPCR of opioid receptors which are mainly designated as mu, delta and kappa receptors.

Are they safe?

Certainly, they are not completely safe.

The main problem with the opioids is their euphoria and subsequent addiction. Morphine is one the drug with high analgesic activity as well as significant euphoria. Heroin is a synthetic opioid with high tendency of drug abuse and addiction.

Another problem with opioids is their respiratory depression. So these drugs should be given with caution at optimal dose to prevent precipitation of respiratory depression.


So even though few drugs do not bind to GPCR, still a large variety of drugs act on GPCR making these receptors clinically more important. Development of selective ligands binding to these receptors brings a great development in the pharmacotherapy of major disorders. Let’s hope more ligands come out in near future adding into the above list and bringing an efficient.