A drug or other substance that affects how the brain works and causes changes in mood, awareness, thoughts, feelings, or behavior. Depending on the substance, psychoactive drugs can cause euphoria, increased energy, sleepiness, hallucinations, and more. Examples of psychoactive substances include alcohol, caffeine, nicotine, marijuana, and certain pain medicines. Many illegal drugs, such as heroin, LSD, cocaine, and amphetamines are also psychoactive substances. Also called psychotropic substance.

1. TOPIC - PSYCHOACTIVE
DRUG
PRESENTED BY
MOHAMMAD OVAIS
M.PHARM 1ST SEM
DEPARTMENT OF PHARMACEUTICAL
CHEMISTRY

2. • A drug or other substance that affects how the brain works and causes
changes in mood, awareness, thoughts, feelings, or behavior.
• Depending on the substance, psychoactive drugs can cause euphoria,
increased energy, sleepiness, hallucinations, and more.
• Examples of psychoactive substances include alcohol, caffeine,
nicotine, marijuana, and certain pain medicines.
• Many illegal drugs, such as heroin, LSD, cocaine, and amphetamines
are also psychoactive substances. Also called psychotropic substance.
INTRODUCTIO
N

3. Types of Psychoactive Drugs
Psychoactive drugs fall into different categories, depending on what effects
the drug has on a person. These include:-
1. Depressants: These drugs can calm the brain, cause sleepiness, and
make a person feel relaxed. However, they can also
cause nightmares, anxiety, and aggression. Alcohol is an example of a
depressant.
2. Stimulants: These include drugs such as cocaine and caffeine.
Stimulants can increase energy, alertness, and wakefulness.

4. 3. Opiates: These are pain-killing drugs that increase feelings of happiness
or euphoria and create a tranquilizing effect. They can lead to addiction
if a person misuses them, and they include drugs such as heroin.
4. Hallucinogens: These drugs can cause a person to have hallucinations,
which means they may see or hear things that are not there. They can
also cause a person to perceive time differently, feel detached from their
surroundings, or feel deeply insightful. LSD is an example of a
hallucinogen.

5. DEPRESSANT
Depressant substances reduce arousal and stimulation. They can affect concentration
and coordination and slow down a person’s ability to respond to unexpected situations. In small
doses, they can cause a person to feel more relaxed and less inhibited.
In larger doses they can cause drowsiness, vomiting, unconsciousness and death.
Benzodiazepine
Mode of action: Benzodiazepine receptors are present in brain and they form a part of GABAA
receptor’s chloride ion channel macromolecular complex. Binding of benzodiazepines to these
receptors produces activation of GABAA receptor and increases chloride conductance by
increasing the frequency of opening chloride ion channel.
 Hyper-polarization–block depolarization- decrease neural excitment

6. Benzodiazepine drug and their Chemical Structure
Benzodiazepine

7. Triazolo Benzodiazapines

8. SAR of Benzodiazaoene
• The presence of electron withdrawing substituents (Cl, F, Br, NO2) at position C-7 is required
for the activity, and the more electron withdrawing substituents leads to potent activity.
• Position 6, 8, and 9 should be unsubstituted for the activity.
• Phenyl or pyridyl at the C-5 position promotes activity. If the phenyl ring substituted
with electron withdrawing groups at 2’ or 2’, 6’ position, then the activity is increased.
On the other hand, substituents at 3’, 4’, and 5’ positions decreases activity greatly.
• Saturation of 4, 5 double bond or shift of it to the 3, 4 position decreases the activity.
• Substitution at N1 by alkyl, halo alkyl, and amino alkyl group increases the activity.
• Reduction of carbonyl function at C-2 position to CH2 yields less potent compound.

9. BARBITURATES
Barbiturates are derivatives of barbituric acid. Their hypnotic activity is conferred by the
replacement of H-atom attached to the C-5 position by aryl or alkyl radicals.
Mode of action: Barbiturates primarily act on GABA benzodiazepin receptor Cl– channel complex and
potentiate GABA ergic inhibitory action by increasing the lifetime of Cl– channel opening induced by
GABA.
Barbiturates do not bind to benzodiazepine receptor promptly, but it binds to another site on the same
macromolecular complex to exert the GABA ergic facilitator actions. The barbiturate site appears to be
located on α and ß subunit. At high concentrations, barbiturates directly increases Cl– conductance and
inhibit Ca2+ dependent release of neurotransmitters and they also depress glutamate-induced neuronal
depolarization.
BARBITURATES

10. SAR of Barbiturates
• Both hydrogen atoms at C5 must be substituted.
• The sum of the carbon atoms of both the substituents at c-5 should be between 6 and 10, in order to
attain optimal hypnotic activity. This sum is also an index of the duration of action.
Sum of value Duration of action
7–9 Rapid onset and shortest duration
5–7 Intermediate duration of action
4 Slowest onset and longest duration
• Introduction of a halogen atom into the C-5 substituents increase potency
• Introduction of a polar substituents (OH, NH2, COOH, CO, RNH, and SO3H) into the aromatic group at
C-5 results in decreased lipid solubility and potency.
• Alkylation at 1 or 3 position may result in compounds having shorter onset and duration of action since
N-methyl group reduces acidity value.
• Replacement of oxygen by Sulphur atoms at C-4 and C-6 position reduces the hypnotic activity.

11. ALCOHOLS
Mode of action: These drugs elicit the action and is similar to the mechanism of barbiturates. These are
general CNS depressants, which produce profound hypnosis.
Metabolism: These are metabolized by alcohol dehydrogenase enzyme. Chloralhydrate undergoes oxidation
to chloral and then to an inactive metabolite, trichloroacetic acid, via aldehyde dehydrogenase,
which also is extensively metabolized to aryl glucuronides via conjugation with glucuronic acid and then
excreted in urine.

12. New generation Depressant Drug

13. STIMULANT
Stimulants Drugs that excite neural activity and speed up body functions Include: caffeine, nicotine, amphetamines,
and cocaine All are mildly addictive. Used to feel alert, lose weight, boost mood or improve athletic performance
β–Phenylethylamine derivatives (Amphetamine and related drugs)
Amphetamine
Amphetamine
Amphetamines/Meth Drugs that stimulate neural activity, speeding up body functions, with associated energy and
mood changes Includes: speed, uppers, and methamphetamines Mimic adrenaline & dopamine Can cause
irreversible changes in mood & function by reducing dopamine receptors & transporters. Withdrawal causes
fatigue, deep sleep, intense depression, increase in appetite.

14. Mechanism of Action of Amphetamine
Amphetamine is an indirect-acting dopaminergic and noradrenergic agonist ; that is, amphetamine causes an increase
in the synaptic concentrations of these neurotransmitters. The central stimulant act ions of amphetamine primarily
involve the dopamine system; amphetamine enhances the release of dopamine and, to a lesser extent , prevents the
reuptake of dopamine into presynaptic terminals
SAR OF AMPHETAMINE

15. METHYLXANTHINE DRUGS
Mode of action: These agents have mild stimulant action and increase the epinephrine secretion and enhance the
neural activity in several areas of the brain. These agents act by producing antagonism of adenosine receptor.
Adenosine is a neuromodulator, which infl uences numerous functions in the CNS and the blocking is responsible for
stimulation.

16. CAFFEINE
Caffeine Stimulant found in coffee, chocolate, tea, and some soft drinks Provides user with a sense of increased
energy, mental alertness, and forced wakefulness Blocks neurological receptor sites that if activated, sedate the central
nervous system Withdrawal symptoms are sleepiness, fatigue, anxiety, insomnia, increased heart rate.
Caffeine is often used as it occurs in brewed coffee, In most subjects, a dosageof 85 to 250 mg of caffeine acts as
a cortical stimulant and facilitates clear thinking and wakefulness, promotes an ability to concentrate on the task at
hand, and lessens fatigue. As the dose is increased, side effects indicating excessive stimulation (e.g., restlessness,
anxiety, nervousness, tremulousness)
CAFFEINE

17. NICOTINE
Nicotine Stimulant found in tobacco Effects similar to those of caffeine – reduces fatigue & drowsiness and
increases mental alertness (epinephrine & norepinephrine) Affects various areas in the brain affecting mood,
decreasing anxiety & reducing pain (Dopamine & Opioids) Very addictive and does not stay in the body very long –
Only takes 7 seconds for nicotine to act on the brain after inhaling.
MECHANISM OFACTION
Nicotine is a stimulant drug that acts as an agonist at nicotinic acetylcholine receptors. These are ionotropic
receptors composed up of five homomeric or heteromeric subunits. In the brain, nicotine binds to nicotinic
acetylcholine receptors on dopaminergic neurons in the cortico-limbic pathways. This causes the channel to open and
allow conductance of multiple cations including sodium, calcium, and potassium. This leads to depolarization, which
activates voltage-gated calcium channels and allows more calcium to enter the axon terminal. Calcium stimulates
vesicle trafficking towards the plasma membrane and the release of dopamine into the synapse.

19. Summary
Psychoactive drugs alter the way a person thinks, acts, and feels.
They often fit into one or more categories, including stimulants, depressants,
opiates, and hallucinogens.
• Stimulants may cause someone to feel a sense of euphoria, excitement,
orincreased energy.
• Depressants can make people feel sleepy, relaxed, or calm.
• Opiates can cause euphoria and have a tranquilizing effect.
• Hallucinogens can alter a person’s senses and cause them to see or hear
things that are not there.
• Different drugs have varying risks, but some are common among
psychoactive drugs. Some of these risks include heart issues, addiction,
worsening symptoms of mental illness, and death.