Phr124

Drug Discovery and Development

Shalimar A. Macababbad, RPh
Pharmacy Instructor
St. Paul University Philippines – College of Pharmacy
 Drug Discovery
and Development
Provide an overview about how a drug
is discovered, the amount and types of
laboratory tests that are performed,
and the conduct of clinical trials before
a drug is ready to be registered for
human use.
• An active ingredient that is intended
to furnish pharmacological activity
or other direct effect in the
diagnosis, cure, mitigation,
treatment, or prevention of a
disease.
• To affect the structure of any
function of human body.
• Are Prescription (Rx) drugs that
require prescription by Physician

1. The only person/s authorized to issue a prescription?

A. Physician
B. Dentist
C. Veterinarian
D. AOTA
• Can be purchased from pharmacies
without prescription
• Mainly established drugs that are
considered safe enough to be taken
without supervision by a Physician
 Drug Development: Clinical Trials in
Drug Discovery:
Methodologies following Humans: protocols
targets & Good Laboratory following Good Clinical
receptors, small Practice, Practice Marketing
molecule drugs, Pharmacodynamics,
application
Pharmacokinetics,
large molecule
Toxicology, Drug
drugs Delivery Systems

Manufacturing:
procedures following
Good Manufacturing
Practice

Compliance with
regulatory
requirements is
necessary

Figure 1. The stages from drug discovery to marketing approval

 Historical approaches in drug
discovery
• Today’s medicine is based on
traditional medicine.
• The most famous ones are
traditional Chinese medicine in East
Asia, Ayurvedic medicine in India,
and formerly Galenic medicine in
Europe, having same resemblance to
each other (Vogel 1991).
 Medicinal chemistry
• Morphine and papaverine from
Papaver somniferum for synthetic
analgesics and spasmolytics
1. The prototype narcotic antagonist is:
A. Nalorphine
B. Naloxone
C. Levallorphan
D. Meperidine

2. The healthcare provider administered Naloxone for a patient at the Emergency room.
Which of the following physical assessment data would be the
most important to indicate that the drug has been effective?
A. Absence of fever
B. Seizure activity stopped
C. Respiratory Rate has normalized
D. Chest pain is better
 Medicinal chemistry
• Atropine from Atropa belladonna for
synthetic spasmolytics
 Medicinal chemistry
• Cocaine from Erythroxylon coca for
synthetic local anaesthetics
 Medicinal chemistry
• Quinine and quinidine from Cinchona
succirubra (Red cinchona) for
synthetic anti-malaria drugs and
antiarrhythmics

1. Major Adverse Effect of Quinine? _______________________

2. What Class of the Anti-Arrhythmic Drugs
does Quinidine belong? __________
 Class I Class II Class III Class IV
“-lol”
IA: Ami D
__________LOL
Quini Bre V
_________________LOL
Pro ______________________LOL I
Di So
Dof
IB:
Lid
Me
To
Ph

IC:
Mor
F
P
Anti-Arrhythmic Drugs - Classes
 Medicinal chemistry
• Ergot alkaloids from Claviceps
purpurea for semisynthetic ergot
derivatives
 Medicinal chemistry
• Reserpine and ajmaline from
Rauwolfia serpentina for synthetic
antihypertensives and
antiarrhythmics
 Medicinal chemistry
• Physostigmine from Physostigma
venenosum for potential
antidementia drugs
 Medicinal chemistry
• Glycosides from Digitalis lanata and
Digitalis purpurea for semisynthetic
cardiac glycosides
 Medicinal chemistry
• Anthraquinones from Senna
angustifolia or Rhamnus frangula or
Rheum officinale for synthetic
laxatives.
 Pharmacological research
• With the emergence of synthetic
chemistry the pharmacological
evaluation of these products for
therapeutic indications became
necessary. Many new drugs were
discovered by this classical approach
during the 20th century.
 Classical way of
Pharmacological Screening
• Sequential testing of new chemical
entities or extracts from biological
material in isolated organs followed
by tests in whole animals.
 Receptor Binding Assays
• Approach for compound evaluation
by the development of radioligand
binding assays, based on evaluation
procedures and mathematical
calculations.
• Described for various transmitters as
well as assays for ion channels and
neurotransmitter reporters.
 Ligand Binding Assay
• Powerful tool in the search for
agonists and antagonists for novel
receptors, and for identification of
novel classes of agonists and
antagonists for known receptors.
 Ligand Binding Assay
AGONIST ANTAGONIST
- Have _________________ - Have _________________
- Have - Have
_________________________________ NO_____________________________
- Mimic the action of ____
endogenous compounds - Block the effect of Agonist
Advantages of Classical Approach
• If a compound has blood pressure lowering
activity in hypertensive rats after oral
dosage, the chances of activity in humans
are high.

• Measurement of dose-response-curves,
effects over a given period of time and
comparison of the effects after intravenous
and oral administration already give hints
for pharmacokinetic data.
Advantages of Classical Approach
• Pharmacokinetic Data
Disadvantages of Classical Approach
• Time consuming and requires
relatively large amounts of the new
compound (usually about 5 g).

• Provides little information about the

molecular mechanisms involved in
the observed effects.
One has to admit that not all breakthroughs
were achieved by the classical way of drug
research. Several drugs have been identified
by serendipity in the clinic/laboratory.
Once the researchers have confirmed that Streptomyces
sp. A1-08 is a new species, they will name it “Streptomyces
mayonensis A1-08” in honor of our country.
 References
• Ng, R. (2004). Drugs From Discovery to Approval. John
Wiley & Sons, Inc.

• Vogel, H. G. (2002). Drug Discovery and Evaluation:

Pharmacological Assays. Springer Publishing.

• World Health Organization