TOPIC - Psychoactive drug.pptx

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 1 st 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. INTRODUCTION

3. Types of Psychoactive D rugs Psychoactive drugs fall into different categories, depending on what effects the drug has on a person. These include:- 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. 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 GABA A receptor’s chloride ion channel macromolecular complex. Binding of benzodiazepines to these receptors produces activation of GABA A 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 N 1 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 Ca 2+ 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 OF ACTION 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.

18. 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.