Lecture for B pharm, Medicinal chemistry of Purbanchal University of Nepal

1. Psychotropic Agents
These are drugs that cure mental disorders.
Mental disorders includes abnormal changes in
how a person feels, acts, thinks or perceives
which degrades ability to function in ordinary
life or socialize with others
– Anxiolytic
– Antidepressents
– Antiphycotics

2. Anxiolytics
Drugs that cause mental clamness

3. Anxiety
• Anxiety is a normal fear response to stress or
threats. It helps us to prepare for a “fight or
flight” action
• Too much or unnecessary anxiety can cause
stress related disorders ranging from
cognitive block to pain and heart palpitations
(abnormal heart beat)

4. Types of Anxiety
• General Anxiety
• Obsessive Compulsive Disorder
• Panic Disorder
• Post Traumatic Stress Disorder
• Specific Phobias
• Social Anxiety

5. Is anxiety really a disease? Yes
Clinical effects of General Anxiety
• Constant worrying or obsession about small or large
concerns
• Restlessness and feeling on edge
• Fatigue
• Difficulty concentrating or your mind "going blank"
• Irritability
• Muscle tension or muscle aches
• Trembling, feeling twitchy or being easily startled
• Trouble sleeping
• Sweating, nausea or diarrhea
• Shortness of breath or rapid heartbeat

6. Drugs used to treat Anxiety are
1) Benzodiazepines:
– Chordiazepoxide, Clonazepam,
– Alprazolam, Diazepam*, Lorazepam
2) Azapirones - Buspirone

7. Chlordiazepoxide
• It is a long acting benzodiazepam
• It has amnestic, anticonvulsant, anxiolytic, hypnotic
and skeletal muscle relaxant properties
• It has an intermediate onset of action (15-30 mins),
with a peak blood level occurring two to four hours
after oral administration. It has active metabolite
• Used for the short-term (2–4 weeks) treatment of
anxiety
• It’s long term use can cause depression, tolerance and
dependence with withdrawal effects similar to alcohol
• MOA- Anxiolytic effect is due to CNS depression caused
by stimulation of GABAA receptors

8. Clonazepam
• It is a intermediate acting benzodiazepam
• It has amnestic, anticonvulsant, anxiolytic, hypnotic and
skeletal muscle relaxant properties
• It has an intermediate onset of action (15-30 mins), with a
peak blood level occurring one to four hours after oral
administration
• Used for the short-term (2-4) treatment of panic disorder
(recurring panic attacks- palpitations, shaking and chest
pain)
• It’s long term use can cause depression, tolerance and
dependence with withdrawal effects similar to alcohol
• MOA- Anxiolytic effect is due to CNS depression caused by
stimulation of GABAA receptors

9. Azapirones: Buspirone
• Azapirones are a class of drugs having both anxiolytics and
antipsychotics activity
• Anxiolytic action due to agonism at serotonin (5-HT]) type
1A receptor
• antipsychotics activity is due to antagonism at D2 receptor
• It has delayed onset of action but
• As potent as diazepam with no tolerance and addictiveness
and no sedative effects, no cognitive or motor impairment
• They are very especially safe and effective in elderly
patients
• Used limited for mild to moderate anxiety and not useful in
severe cases like panic attack

10. Thanks

11. Review
How to they point out SAR of drugs?

12. Comparative oral doses of various Benzodiazepams

13. • SAR is developed by analyzing activity of a series of
drugs with a small alteration made around a common
structure
• These alteration must be planned carefully so that
effective comparisons can be made
• We can judge in above compounds that
– Substituting Nitrogen decreses activity (1st and 2nd)
– Removing hydroxyl group improves activity (1st and 4th)
– Having an extra aromatic nitrogen ring is good and
compensates lack of Chlorine in lower ring(6th and 7th)
– We know that for diazepams, having electronegative
groups at specific positions is essential for activity and it
reflected in these 8 marketed compounds but to include it
as a valid SAR we need to compare it’s activity with those
structures that lack those electronegative groups
• But these small alteration have big changes in ADME

15. Assignment
• Refer the given research article and point out
SAR of drugs called HDAC inhibitors
• European Journal of Medicinal Chemistry 44
(2009) 1067e1085
• Key skill gained:
• Knowledge on various structural diversity that
can be implemented for drug design