Muscarinic Agonist

DRUGS PHARMACOPHORE CORRESPONDING USE/S ADVERSE EFFECT/S

ACTIVITY
Methacholine Ethylene group High muscarinic Diagnostic agent 1. Headache 
Chloride activity with little for Asthma 2. Sore throat
(Provocholine) or no nicotinic 3. Lightheadedness
4. Nausea, 
5. Vomiting
or dizziness

Bethanechol Ethylene group High muscarinic Relief of urinary 1. Dizziness or

(Urecholine) activity retention and drowsiness
abdominal 2. Headache
distention after 3. Nausea
surgery. 4. Vomiting
Acyloxy group 1. More resistant 5. Diarrhea
to hydrolysis 6. Flushing
2. ↑ Duration of 7. Sweating
action 8. Teary eyes.

Carbachol Acyloxy group 1. More resistant Reduce the 1. Headache

(Miostat) to hydrolysis intraocular tension 2. Stomach cramps
2. ↑ Duration of of glaucoma and 3. Vomiting
action during Ocular 4. Diarrhea
surgery 5. Mild eye
irritation
6. Increased
sweating
7. Urination.

Pilocarpine (still unknown) (still unknown) Management of 1. Sweating 

Hydrochoride glaucoma 2. Nausea
(Salogen) 3. runny nose
4. Chills
5. Flushing
6. Frequent
urination
7. dizziness 
8. weakness
9.  diarrhea
Cevimeline (still unknown) (still unknown) Treatment of dry 1. Sweating
Hydrochloride mouth associated 2. Nausea
(Evoxac) with Sjögren 3. Runny nose
syndrome 4. Flushing
5. Frequent urge to
urinate
6. dizziness 
7. weakness
8. diarrhea
9. Teary eyes

NEUROTRANSMITTER RELEASERS INHIBITORS

DRUGS PHARMACOPHORE CORRESPONDIN USE/S ADVERSE
G ACTIVITY EFFECT/S
Amphetamine
1. β - phenethylamine Given Anorexiant, High addiction
peripherally, Tx. of ADHD liability,
lacks central DOC for euphoria,
activity. narcolepsy paranoia,
aggression,
insomnia,
hypertension
2. amino group Increases CNS
rather than
peripheral
activity.

Phenylpropanolamine β -hydroxyl group Decreasing the Decongestant Nervous

ability to cross anorexiant system
the blood brain stimulation,
barrier. resulting in
tremor,
anxiety,
insomnia,
dizziness, and
nervousness.
Headache
may also
occur
Ephedrine
β -hydroxyl group Less lipophilic Tx. of Euphoria,
and less CNS narcolepsy, hypertension
activity idiopathic
postural
hypotension,
enuresis

Methampetamine
1. Methyl group More lipophilic Anorexiant, High addiction
and more CNS Tx. of ADHD , liability,
activity. DOC for euphoria,
narcolepsy paranoia,
2. Amine group Increase CNS aggression,
activity insomnia,
hypertension

Imipramine 1. 2 Carbon units Responsible for Antidepressan Dry mouth

Hydrochloride being t blurred vision
antidepressant headache
drowsiness
2. 2 phenyl rings by a Responsible for dizziness,
central 6 or 7 various CNS constipation,
membered ring side effects due nausea,
to high vomiting, loss
lipophilicity of appetite,
diarrhea,
3. Tertiary amine group Norepinephrine stomach
and Serotonin cramps,
Reuptake weight
Inhibitor gain/loss, and
increased
sweating may
occur
Desipramine Secondary amine group Selective Antidepressan Dry mouth,
Hydrochloride Norepinephrine t blurred vision,
Reuptakte headache,
Inhibitor drowsiness,
dizziness,
constipation,
nausea,
vomiting, loss
of appetite,
diarrhea,
stomach
cramps,
weight
gain/loss, and
increased
sweating may
occur
Thiazide Diuretics
DRUG PHARMACOPHORE CORRESPONDING USE/S ADVERSE
ACTIVITY EFFECT/S
Hydrochlorthiazide 1. 2 Position Can tolerate the Management Sulfonamide-
(Hydrodiuril) presence of of Heart associated
relatively alkyl Failure adverse effects
groups such as
CH3 Management Water and
2. 3 Position Determines of idiopathic electrolyte
potency and DOA imbalanace
of thiazide Nephrocalcino Metabolic side
diuretics sis effects
* certain
substituents in the Management
3 position have of
Chlorthiazide (Diuril) yielded Nephrogenic
compounds that
are relatively Diabetes
specific inhibitors Insipidus
of the diuretic
action of thiazides
*loss of C-C
double bond b/w
3 & 4 position
increase potency
3. 4, 5 & 8 position Direct substitution
diminishes
diuretic activity
Hydroflumenthiazide 4. 6 position 4. Substitution with
(Saluron) an activating group
is essential for
diuretic activity
*best substituents
groups ( Cl- Br - CF3-
NO2- )

5. 7 position 5. Essential for

prerequisite for
diuretic activity

Potassium Sparing Diuretics

DRUG PHARMACOPHORE CORRESPONDING USE/S ADVERSE
ACTIVITY EFFECT/S

Eplerenone (Inspra) 1. Epoxy group 1. more selective for Adjunct in the Hyperkalemnia
mineralcorticoid Management Gynecomastia
receptor of heart failure Loss of libido
Management sterility
2. Presence of 2. Responsible for of diuretic-
Carbomethoxy group diuretic activity induced
hypokalemia
Management
of
hyperaldostero
nism
Management
Spironolactione 1. Presence of 1. Replacement of the of ascites &
(Aldactone) Thioacetyl group Carbomethoxy group peripheral
with Thioacetyl group edema

*less selective due to

the absence of epoxy
group

ACE - INHIBITORS
DRUGS PHARMACOPHORE CORRESPONDING USE/S ADVERSE
ACTIVITY EFFECT/S
Captopril (Capoten) Sulfhydryl/Thiol/Merca ↑ Incidence of taste Antihypertensiv 1. Skin rash
pto group disturbance and skin e agent 2. Taste
rash disturbance
3. Cough
↓ Duration of action 4. Hypotension
5. Hyperkalemia
6. Angioedema

Enalapril ( Vasotec) 1. Ethoxy-1-oxo / 1. ↑ Oral 1. Cough

Esterification of bioavailability 2. Hypotension
carboxylic acid Antihypertensiv 3. Angioedema
e agent 4. Hyperkalemia
2. Phenylalkyl 2. ↑ Inhibition activity

Lisinopril (Zestril) 1. N-butylamine 1. Orally active 1. Cough

2. Hypotension
Antihypertensiv 3. Angioedema
2. Phenylalkyl 3. ↑ Inhibition activity e agent 4. Hyperkalemia

Fosinopril 1. Phenylalkyl 1. ↑ Inhibition activity 1. Cough

(Monopril) 2. 2-Methyl-1- 2. ↑ Oral 2. Hypotension
propanoloxypropoxy / bioavailability Antihypertensiv 3. Angioedema
Esterification of 3. ↑ Potency e agent 4. Hyperkalemia
phosphoric acid
3. Benzene ring

Angiotensin-II-Receptor Blocker
DRUG PHARMACOPHORE CORRESPONDING USE/S ADVERSE
 ACTIVITY EFFECT/S
®
Losartan (Cozaar ) 1. Imidazole ring 1. Vasodilation Fatigue
2. Tetrazole ring 2. Increases Anemia
binding affinity and Antihypertens UTI
oral bioavailability ive agent, Chest pain
intolerance to Diarrhea
3. Biphenyl-methyl group 3. Vasodilation ACEi, MI Hypoglycemia

Valsartan ( Diovan®) 1. Acylated amino acid 1. Better binding Dizziness

affinities BUN
2. Tetrazole ring 2. Increases Antihypertens Hypotension
binding affinity and ive Dizziness
oral bioavailability Agent,
intolerance to
3.Biphenyl-methyl group 3. Vasodilation ACEi, MI

Telmisartan( Micardis® ) 1. Carboxylic acid 1. More potent Upper

Antihypertens respiratory tract
2. Biphenyl-methyl group 2. Vasodilation ive agent, infection(URTI)
intolerance to Back pain
ACEi, MI Myalgia
Sinusitis

Irbesartan ( Avapro ®) 1. Hydroxymethyl group 1. Longer binding Hyperkalemia

to the receptor Dizziness
2. Tetrazole ring 2. Increases Antihypertens URTI
binding affinity and ive agent, Orthostatic
oral bioavailability intolerance to hypotension
ACEi, MI Fatigue
3. Vasodilation
3. Biphenyl-methyl group
Candesartan ( Antihypertens Dizziness
Ata cand ®) 1. Benzimidazole 1. Stronger blood ive agent, Tiredness
pressure lowering intolerance to Lightheadednes
ACEi, MI s

2. Tetrazole ring 2. Increases

binding affinity and
oral bioavailability

3. Biphenyl-methyl group 3. Vasodilation

Olmesartan ( Benicar®) 1. Imidazole ring that 1. Potent Dizziness

have hydroxymethyl and antagonistic effect Fatigue
 carboxy group Antihypertens Diarrhea
2. Tetrazole ring 2. Increases ive agent, HA
binding affinity intolerance to Hyperglycemia
ACEi, MI
3. Biphenyl-methyl group 3. Vasodilation

Nitrates and nitrites

DRUGS PHARMACOPHORE CORRESPONDING USE/S ADVERSE
ACTIVITY EFFECT/S
Isosorbide Dinitrate Nitric oxide Vasodilation activity Anti anginal Headache
(Isordil) Feeling light
headed
Low Blood
Pressure

Tetra Erythrityl Nitric oxide -Vasodilation activity Anti anginal Throbbing

tetranitrate headaches
Dizziness

Nitroglycerin Nitric oxide Vasodilation acitivity Treat Headache

(Nitrostat) episodes Weakness
of angina (c Dizziness
hest pain). Lightheadedness
Nausea
Flushing
Amyl nitrite Nitric oxide Vasodilation activity Relieve the Headache
pain of Weakness
angina Dizziness
attacks. Lightheadedness
Nausea
Flushing
Shortness of
breath
Nausea and
vomiting
Cold sweat
Pale skin

Potassium channel blocker

DRUGS PHARMACOPHORE CORRESPONDING USE/S ADVERSE EFFECT/S
ACTIVITY
Amiodarone - Iodine group - Reduce the risk - Paroxysmal faster/slower/more
of organ adverse supra-ventricular irregular heartbeat
effects tachycardia
(paroxysmal SVT) Severe dizziness
-Recurrent
ventricular Fainting
fibrillation
-Supra-
ventricular
arrhythmias
-Unstable
ventricular
tachycardia
-Recurrent supra-
ventricular
tachycardia
Dofetilide (Tikosyn) Phenyl ring -Increase the effect -Anti-arrythmic Headache
(atrial
fibrillation/flutter Dizziness
)
Nausea

Antihyperlipedemic Drugs
DRUG PHARMACOPHORE CORRESPONDING USE/S ADVERSE
ACTIVITY EFFECT/S
BILE ACID SEQUESTRANT Divinylbenzene Increase amount of Patients only w/ Constipation
Cholestyramine (Cuemid) copolymer w/ Divinylbenzene to 2 – hyperlipoproten Steatorrhea
quarternary 8% = decrease efficacy emia involving
ammonium eleveated LDL
level

HMG-COA REDUCTASE 1. Lactone ring 1. sensitive to Antihyperlipide Headache

INHIBITOR stereochemistry of it, mic agent Nausea
Simvastatin (Zocor) ability of the ring to Flatulence
hydrolyzed Heartburn
Abdominal pain
2. Bicyclic rings 2. could be replace w/ Rhabdomyolysis
other lipophilic rings
size and shape are
important for activity

3. Ethylene bridge
Lovastatin (Mevacor) 3. responsible for its Antihyperlipop Increased
activity roteinemic creatine
agent phosphokinase
Flatulence
Nausea
Rhabdomyolysis

Atorvastatin (Lipitor)  Primary  Headache

hyperlipide  Flatulence
mia and;  Diarrhea
 secondary  Rhabdomyo
hypercchol lysis
esterolemia

FIBRIC ACID DERIVATIVES 1. Isobutyric acid 1. Essential for

Fibric acid grp activity  Rhabdomy
2. 3-substitution at 2. Produce olysis
p-position of compounds w/  Bile stone
aromatic ring w/ longer half life formation
chloro or 3. Results in an  N&V
chlorine cont’ng active drug
isopropyl ring
 3. Compounds
conating n-
propyl as a
spacer grp

Fenofibrate (Artiflex) 1. fenofibrate 1. becomes prodrug  Hypertriglyc

contain ester eridemia  Arthralgia
 Hyperlipide  Diarrhea
2. second aromatic 2. imparts greater mia  Cough
ring lipophilic than
clofibrate resulting
more potent
hypocholesterolemic
& triglyceride-
lowering agent

3. Para-substitution 3. Increased half life

w/ Cl or Cl
containing
isopropyl ring

4. n-propyl spacer 4. results in active

in Gemfibrozil drug
drug

Gemfibrozil (Lopid) Reduction  Arthralgia

1. phenolic 1. active metabolite of coronary  Diarrhea
glucuronide grp Heart d/se  Cough
risk

Clofibrate (Atromid S)  Hyperlipidem

ia

Ezetimibe (Ezetrol) Adjunct to
statin/ statin-
tolerated
Patient

Probucol 1. 2-tertiary 1. giving a high  Hyperchole  Prolonged

butylphenol grp lipophilic character w/ sterolemia QT
linked by strong antioxidant intervals
dithiopropylidene properties  Arrhythmia
bridge s
 Anticoagulants
DRUGS PHARMACOPHORE CORRESPONDING USE/S ADVERSE
ACTIVITY EFFECT/S
Direct Thrombin Inhibitors
Bivalirudin (Angiomax) NH2 terminal Reversibly binds - Anticoagulant in Bleeding
sequence (D-Phe- to thrombin site, patients with Fever
Pro-Arg-Pro) causing inhibition unstable angina  Hypotension
undergoing percuta Syncope
neous  transluminal Cerebral ischemia
coronary angioplas Confusion
ty (PTCA). Facial paralysis
-Heparin Lung edema
induced thrombocy Kidney failure
topenia (HIT) or Oliguria
heparin induced
thrombocytopenia
and thrombosis syn
drome (HITTS)
undergoing PCI.
Lepirudin (Refludan)  heparin-induced Bleeding
thrombocytopenia  hemoperitoneum
(HIT) hemoptysis
liver bleeding
lung bleeding
mouth bleeding
retroperi-toneal
bleeding

Carbachol Acyloxy group 3. More Reduce the 8. Headache

(Miostat) resistant to intraocular tension 9. Stomach
hydrolysis of glaucoma and cramps
4. ↑ Duration during Ocular 10. Vomiting
of action surgery 11. Diarrhea
12. Mild eye
irritation
13. Increased
sweating
14. Urination.
Pilocarpine (still unknown) (still unknown) Management of 10. Sweating 
Hydrochoride glaucoma 11. Nausea
(Salogen) 12. runny
nose
13. Chills
 14. Flushing
15. Frequent
urination
16. dizziness 
17. weakness
18.  diarrhea

Cevimeline (still unknown) (still unknown) Treatment of dry 10. Sweating

Hydrochloride (Evoxac) mouth associated 11. Nausea
with Sjögren 12. Runny
syndrome nose
13. Flushing
14. Frequent
urge to urinate
15. dizziness 
16. weakness
17. diarrhea
18. Teary eyes