Describe the Differences Between Antipsychotic and Antidepressant Drugs, the Efficacy and Common Side Effects of Each Drug.

Scientific name : 7-chloride-1-methyl-5-phenyl-1,3-dihydro-2 H -1,4-benzodiazepine-2-one.

Preparation:

According to the principle of preparation of nitrazepam, in which the starting material is 2-methylamino-5-chlorobenzophenone in ether.

Nature:

White to yellow crystalline powder, odorless; stable in air. Soluble in organic solvents; slightly soluble in water. Melts at 131-135 o C.

Qualitative :

- Diazepam solution in concentrated H 2 SO 4 gives green-yellow fluorescence in 365nm UV light.

- UV absorption: diazepam solution in H 2 SO 4 0.5%/methanol, gives 3 absorption peaks at 242; 285 and 366 nm.

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Quantitative: By methods as mentioned in the general section.

Uses : Sedative; muscle relaxant; active metabolite.

Indications: Anxiety, stress, drunkenness, skeletal muscle spasms.

Dosage: Adults, take 2-10 mg/time x 2-4 times/24 hours; reduce dose for children.

Acute: Intravenous injection 2-25mg/time.

Storage : Protect from light.

LESSON 3. MEDICATIONS FOR TREATING MENTAL DISORDERS

Target

1. Describe the differences between antipsychotic and antidepressant drugs, the effectiveness and common side effects of each drug. Antipsychotic drug management regimen.

2. Present the structure, physical and chemical properties, general testing methods. Preparation methods of some typical drugs.

3. Present the formula, physical and chemical properties, testing, and uses of typical drugs.

CONTENT

1. MEDICATIONS FOR TREATING MANIC PSYCHOLOGY

This drug is also known as “psychotropic drug”, used to treat symptoms of increased mood, paranoia, and hallucinations in manic psychosis or manic phase in alternating manic-depressive psychosis… Bringing the patient back to a state of mental balance.

Classify:

According to structure, drugs are divided into several groups:

- Phenothiazine derivatives.

- Thioxanthene derivatives.

- Butyrophenone derivatives.

- Other structural drugs and lithium carbonate.

1.1. Phenothiazine derivative drugs

General formula:

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General physical and chemical properties:

S

6

7

8

9

4

3

2

1

5

10 R 2

N

R 1

All substances have a tertiary amine group, so they are basic; the base form is non-crystalline and insoluble in water. Usually used as hydrochloride salt or salt with other acids. All are white crystals, difficult to dissolve in organic solvents; easily discolored by light; irritating to skin and mucous membranes on contact.

Chemical and qualitative properties:

- Phenothiazine nucleus is easily oxidized even with air oxygen; when exposed to strong oxidizing agents such as H 2 SO 4 , HNO 3 , the reaction occurs quickly, giving color.

- The preparation solution in water precipitates with the common alkaloid reagent.

- Physical methods: SKLM, IR spectrum, UV absorption...

Quantitative method:

The preparations are hydrochloride salts, determined by two methods:

1. Acid-base method in anhydrous acetic acid solvent; 0.1M HClO 4 standard solution ; potentiometric indicator (or color indicator).

2. Acid-base method in 96% ethanol solvent; 0.1M NaOH standard solution in water or ethanol; potentiometric indicator.

Effect:

Phenothiazine derivatives block postsynaptic dopamine receptors causing paralysis. In addition, the drugs also have sedative and mild antihistamine effects.

Undesirable effects:

The most significant side effects of phenothiazine derivatives are extrapyramidal reactions with symptoms: Parkinson's-like hand tremors; involuntary motor movements such as wry neck, muscle twitching, restlessness, akathisia, and stiff hands.

Other effects: Lethargy, dry mouth, decreased vision, nausea, urinary retention.

Storage and administration: Protect from light, administer as directed by a psychotropic drug regimen.

1.2. Thioxanthene derivatives

Structure:

General formula:

6 5

10

4

7

3

2

8

9

1

S

R 2

R 1

Drug list: Thiothixen, Cloprothixen, Flupenthixol.

General physical and chemical properties:

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Usually used in base or hydrochloride salt form. Discolors when exposed to light and air; reacts with oxidizing reagents to produce colored decomposition products; absorbs UV…

Effect: Similar to phenothiazine derivatives in psychotropic effects.

Storage and handling: Protect from light; handle as directed by a psychotropic drug regimen.

1.3. Butyrophenone derivatives

General formula:

(R and Z are substituents)

Effect: Paralytic and antiemetic.

Undesirable effects:

RC CH 2 CH 2 ZO

Extrapyramidal effects are more common than with phenothiazine derivatives.

Drug list: Haloperidol, Benperidol, Fluanison, Pipamperon, Trifluperidol.

1.4. Drugs with other structures

Drug list: Loxapine, Clozapine, Carbamazepine, Risperidone.

CHLOPROMAZINE HYDROCLORIDE

Brand name: Aminazin, Plegomazin.

Recipe:

C 17 H 19 ClN 2 S.HCl

S

CH 2 CH 2 CH 2

.HCl

CL

CH 3

N

CH 3

ptl: 355.32

Scientific name: 2-chloro-10-(3-dimethylaminopropyl)-phenothiazine hydrochloride.

Preparation: Properties:

White crystalline powder, odorless, bitter taste; discolored when exposed to light and air for a long time; slightly hygroscopic. Melting point: about 196ᵒC.

Easily soluble in water, soluble in ethanol; poorly soluble in many organic solvents.

UV absorption, giving two absorption maxima at 254 and 306 nm.

Chemical and qualitative properties: As mentioned in the general section.

Quantification: By acid-base method (see general section).

Uses:

Oral or injected treatment of manic depression. In addition, the drug is also used as an anti-allergy and to reduce mild seizures.

Adults, take 25 - 50 mg/time, 2 - 3 times/24 hours; intramuscular injection 25 - 50 mg/24 hours.

Undesirable effects: as mentioned in the general section.

Contraindications: Parkinson's disease, neurological disorders; drug hypersensitivity.

Storage: Protect from light; psychotropic drugs.

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HALOPERIDOL

Brand name: Haldol, Aloperidin.

Recipe:

C21H23ClFNO2​​​​​

FC CH 2 CH 2 CH 2 N O

OHCl​

ptl: 375.78

Scientific name: 4-[4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl]-1-(4-fluorophenyl) butane- 1-one.

Preparation: Condensation of 4-(p-chlorophenyl)-4-piperidinol (I) with 4-chloro-4-fluorobutyrophenone

(II) in toluene; extract haloperidol and recrystallize in diisopropyl ether or other suitable solvent:

COUGH

CL

NH + Cl

CH 2

CH 2

CH 2 CO

F- Haloperidol HCl

Nature:

White, odorless crystalline powder; discolored in light; melts at about 150ᵒC. Slightly soluble in water, increased solubility by addition of lactic acid; soluble in ethanol, methanol.

Qualitative:

- UV absorption peaks at 245 nm (0.002% solution in 0.1M HCl).

- Haloperidol solution in ethanol; add dinitrobenzene and KOH reagents in ethanol, purple color turns reddish brown.

- Thin layer chromatography, compared with haloperidol standard.

Quantitative:

Uses: Paralytic effect, does not cause sleep.

Indications: Manic psychosis.

Adults, take 5 - 100 mg/24 hours, divided into 2 - 3 times. Acute cases: intramuscular injection of 5 mg/ml solution.

Adverse effects: Similar to phenothiazine derivative psychotropic drugs.

Storage: Protect from light, administer as directed by a psychotropic drug regimen.

2. MEDICATIONS FOR THE TREATMENT OF PSYCHOLOGICAL DEPRESSION

Symptoms of depression include deep depression, paranoid self-esteem, motor inhibition, and extreme despair. Stimulants that increase central nervous system transmission can help overcome depression.

Classification: antidepressants are divided into 4 groups: Group 1: tricyclic drugs.

Group 2: biologic monoamine oxidase inhibitor (MAOI).

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Group 3: selective serotonin reuptake inhibitors. Group 4: unclassified drugs.

2.1. Tricyclic drugs

Effect: anti-anxiety and depression symptoms.

Adverse effects: Dry mouth, constipation, visual disturbances. Change to manic phase when exceeding therapeutic dose.

2.2. Drugs that inhibit the enzyme that oxidizes biological monoamines.

(MAO, stands for Monoamine Oxidase Inhibitors).

Effect:

Inhibits the enzyme that oxidizes and breaks down neurotransmitters monoamines, increases the concentration of these amines at the synapse, and increases the speed of conduction.

Undesirable effects: often causes hypotension.

2.3. Selective serotonin reuptake inhibitors. (SSRI = Selective Serotonin Reuptake Inhibitors). Effects:

Selective inhibition of postsynaptic serotonin reuptake, increases central neurotransmission, antidepressant.

Undesirable effects:

Causes gastrointestinal disorders because the digestive tract uses more serotonin than other tissues; however, this effect does not occur frequently, so the drug has a high safety profile and is the preferred choice in treatment. There may also be adverse effects like the tricyclic group of drugs, but they are not significant.

2.4. Unclassified drugs (Heterocyclic)

Low efficacy so not the first choice drug in psychiatric treatment; only used as a substitute when other drugs are ineffective.

General physical and chemical properties:

- Most substances have an amino group in the molecule, basic properties; pharmaceutical form is base or hydrochloride salt.

- Tricyclic frameworks and similar structures are not resistant to oxidizing agents and are susceptible to discoloration when exposed to air and light for long periods of time.

Qualitative: By physical methods: IR spectrum, chromatography, UV absorption.

Quantitative: Apply one of the following methods:

1. Acid – base in anhydrous acetic acid; standard solution is 0.1M HClO 4 ; measure potential.

2. Acid – base in 96% ethanol; standard solution is 0.1M NaOH; measure potential (applicable to hydrochloride salt form).

3. UV spectroscopy: applicable to dosage forms.

IMIPRamine Hydrochloride

Brand name: Melipramin, Tofranil.

Recipe:

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C19H24N2.HCl​​​​​​

NH2C​​

CH 2

CH 2

CH 3 N CH 3

.HCl

ptl: 316.87

Scientific name: 5-(3-dimethylaminopropyl)-10,11-dihydro-5H-dibenz [b,f] azepine hydrochloride

Preparation:

Properties: White to yellow crystalline powder, odorless; easily discolored in air and light. Melting point: about 172ᵒC. Easily soluble in water, ethanol; soluble in acetone, almost insoluble in ether, benzene.

Chemical properties: Basic and reducing properties.

Qualitative:

- Dissolve the test substance in concentrated HNO 3 to give a deep red color.

- Solution for precipitation with alkaloid reagent and reaction of chloride ion.

- UV spectrum: absorption maximum at 251 nm, E (1%,1cm) about 260 (0.002% solution in 0.01M HCl).

Quantitative: Acid-base method in 96% ethanol solvent.

Uses: Tricyclic drug, treatment of mental depression.

Adult dosage:

Acute: intramuscular injection 25 – 100 mg/24h. Maintenance, oral 25 mg/time, 3 times/24h.

Storage: Protect from light, administer as directed by a psychotropic drug regimen.

FLUOXETINE HYDROCLORIDE

Brand name : Fluoxiben, Lovan.

Recipe:

CF 3 O HC

C2H5NHCH3​​​​​

.HCl

Nature:

C 17 H 18 F 3 NO

ptl: 345.79

White or almost white crystalline powder. Slightly soluble in water and alcohol.

Uses: SSRI antidepressant.

Indications: depression.

Dosage:

Adults, take 20 - 80 mg/24 hours in the first days; gradually adjust the dose down in the following days.

Undesirable effects : low level, drug can accumulate. Do not use with IMAO group.

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