Trazodone hydrochloride Uses and synthesis methods |
Uses and mechanism of action |
Trazodone hydrochloride belongs to the triazolopyridine class of antidepressants,and is mainly used to treat various types of depression and anxiety disorders with depressive symptoms,as well as mood disorders after withdrawal in drug addicts.This product is a phenylpiperazine propyl derivative,which has nothing to do with tricyclic or tetracyclic antidepressants in terms of chemical structure.It has no monoamine oxidase inhibitory effect or amphetamine-like characteristics,and has almost no anticholinergic effect.Its exact antidepressant mechanism for the human body has not been fully elucidated yet,but it is generally believed that at therapeutic doses,its antidepressant pharmacological effect is to selectively inhibit the reabsorption of 5-hydroxytryptamine(5-HT),and can have a weak effect of preventing the reabsorption of norepinephrine,but has no effect on dopamine,histamine and acetylcholine,and does not inhibit the activity of monoamine oxidase(MAO)in the brain.Trazodone hydrochloride also has a reinforcing effect on the behavioral changes induced by 5-hydroxytryptophan,the precursor of 5-HT. |
Its antidepressant effect is similar to that of tricyclics and monoamine oxidase inhibitors(MAOI),but it has less toxicity to the cardiovascular system and is more suitable for elderly patients or patients with cardiovascular diseases.It can be well absorbed after oral administration,and the peak plasma concentration occurs about 1 hour after taking it on an empty stomach and 2 hours after taking it with food.The elimination of trazodone hydrochloride is biphasic,including an initial phase(T1/2 is 6h)and a subsequent slow phase(T1/2 is 5-9h).Due to the large variation in the clearance rate of trazodone hydrochloride in the body,some patients may accumulate in the plasma after taking it.This product also has a central sedative effect and a slight muscle relaxant effect,but no antispasmodic and central excitatory effect.This product can cause a drop in blood pressure.With years of clinical experience,its cardiotoxicity is an issue that has attracted more and more attention,and the effect is related to the dose. |
Pharmacokinetics |
Trazodone hydrochloride is well absorbed after oral administration and is not selectively concentrated in any tissue.
The plasma protein binding rate is 85% to 95%. When this product is taken immediately after a meal, food may increase the absorption of the drug,
reduce the maximum blood drug concentration and prolong the time to reach the maximum concentration. When taken orally on an empty stomach,
the maximum blood concentration can be reached in about one hour, while it takes about two hours to take it during or after a meal. |
Trazodone hydrochloride is mainly metabolized extensively by microsomal enzymes in the liver. Chemicalbook
This product and its metabolites are easily passed through the blood-cerebrospinal fluid barrier, but very small amounts pass through the placental barrier,
and the metabolites are finally excreted through the kidneys. The excretion of this product is divided into two phases,
including a faster initial phase (half-life of 3 to 6 hours) and a slower second phase (half-life of 5 to 9 hours), and it is not affected by food.
Because the clearance rate of this product in the body varies greatly from person to person, trazodone hydrochloride may accumulate in the plasma of some patients.
This product can be excreted through breast milk. |
Trazodone |
Trazodone is a triazolopyridine antidepressant with similar effects to tricyclics and MAOI. It can be used clinically to treat depression.
Patients with refractory depression who have not responded to other antidepressants are often effective with this product.
It can also be used to treat anxiety disorders and is more suitable for the treatment of elderly depression or patients with concomitant heart diseases.
The mechanism of action is to selectively block the reuptake of 5-HT and have a weak effect of preventing the reuptake of norepinephrine,
but it has no effect on dopamine,histamine and acetylcholine, nor does it inhibit the activity of MAO in the brain.
It has low toxicity to the cardiovascular system and is more suitable for elderly patients with depression or those with cardiovascular diseases. |
This product also has central sedation and slight muscle relaxation effects, but no antispasmodic and central excitatory effects.
It has no effect on the heart, but can cause a drop in blood pressure and is dose-related. It can be well absorbed after oral administration.
The peak plasma concentration occurs about 1 hour after taking trazodone hydrochloride on an empty stomach, and reaches a peak 2 hours after taking it with food. After absorption,
it is mostly distributed in the liver and kidneys, metabolized by the liver, and the metabolites are still significantly active.
It easily passes through the blood-cerebrospinal fluid barrier, but rarely passes through the placental barrier.
The metabolites are finally excreted through the kidneys.It is rarely excreted in its original form. Renal impairment does not affect its excretion.
The t1/2 is 4.1h. The elimination of trazodone hydrochloride is biphasic,including an initial phase (T1/2 is 6h) and a subsequent slow phase (T1/2 is 5-9h).
Due to the large variation in the clearance rate of trazodone hydrochloride in the body, some patients may accumulate in the plasma after taking it. |
Toxicology |
1) Acute toxicity: The oral LD50 of trazodone hydrochloride is 610 mg/kg for mice, 486 mg/kg for rats, and 560 mg/kg for rabbits. The lethal dose can cause respiratory distress, salivation, collapse, convulsions and other symptoms in animals.
(2) Long-term toxicity: A one-year study of oral doses of 10 mg/(kg.d) to 30 mg/(kg.d) for dogs and 20 to 80 mg/(kg.d) for monkeys did not show organ toxicity caused by trazodone hydrochloride, but some female dogs in the high-dose group had convulsions and death.
(3) Reproductive toxicity: Oral administration of 15-450 mg/(kg.d) to rats and rabbits during the second trimester of pregnancy revealed no teratogenic effects except for stillbirth at a dose of 450 mg/(kg.d); 10-300 mg/(kg.man) was administered to male and female rats before and after mating, respectively, and female rats continued to receive the drug during pregnancy and lactation. Except for a slightly lighter weight of pups at delivery in the high-dose group, there were no adverse effects on fertility, mating ability, pregnancy and postpartum; 10-300 mg/(kg.d) was administered to rats during the last 6-7 days of pregnancy and throughout the lactation period. The results showed that except for a slightly lighter weight of pups at delivery and 21 days of age at high doses, there were no adverse effects on pregnancy, pup survival and mother rat feeding of pups.
(4) Carcinogenicity: Oral administration of 300 mg/Kg per day to rats for 18 months did not show carcinogenicity. |
Adverse Reactions |
Common adverse reactions include drowsiness, fatigue, dizziness, headache, insomnia, tension and tremor, as well as blurred vision,
dry mouth and constipation. Postural hypotension (which can be alleviated by taking the medicine at the same time as meals), tachycardia, nausea,
vomiting and abdominal discomfort are rare. Very few patients experience musculoskeletal pain and dreaminess. In clinical studies,
some adverse reactions have been reported to be related to the use of trazodone hydrochloride: akathisia, allergic reactions, anemia,
flatulence, abnormal urination, sexual dysfunction and menstrual abnormalities. However, they are seen in very few patients. |
Drug overdose |
When this product is used in combination with other drugs (ethanol, ethanol-chloral hydrate-diazepam, amobarbital, methylamine or aminoproline), overdose of trazodone hydrochloride can cause death. The most serious adverse reactions of overdose of this product alone are abnormal penile erection, respiratory arrest, epileptic seizures and abnormal electrocardiograms. Common adverse reactions are drowsiness and vomiting. Overdose can increase the incidence and severity of various adverse reactions.
There is currently no specific antidote. Hypotension and excessive sedation should be treated according to clinical routine. Once an overdose of this product is used, gastric lavage should be performed. Taking diuretics can promote drug excretion. |
Drug Interactions |
1. Patients taking trazodone hydrochloride may increase the plasma concentration of digoxin or phenytoin if they are taking digoxin or phenytoin at the same time.
2. This product may enhance the effects of alcohol, barbiturates and other central nervous system depressants. 3. The interaction between this product and MAOI is not clear at present. If this product is taken just after stopping the drug or taken at the same time, trazodone hydrochloride should be started at a low dose until the clinical effect is achieved.
4. When trazodone hydrochloride is used in combination with antihypertensive drugs, the dose of antihypertensive drugs needs to be reduced. |
Precautions |
1. Those who perform potentially dangerous tasks (such as driving or operating machinery) should be careful during medication.
2. Trazodone hydrochloride should be taken after meals. Taking the drug on an empty stomach may increase dizziness or lightheadedness.
3. Little is known about the interaction between trazodone hydrochloride and general anesthetics. Therefore, trazodone hydrochloride should be discontinued as soon as clinically permitted before elective surgery.
4. Patients taking trazodone hydrochloride occasionally experience a decrease in total white blood cell count and neutrophil count. If the white blood cell count is lower than the normal range, the drug should be discontinued for observation. For patients who develop fever or sore throat or other symptoms of infection during treatment, it is recommended to check the white blood cell and differential counts.
5. Use with caution in patients with epilepsy and those with poor liver and kidney function. [Use in pregnant and lactating women] For pregnant women, there is no sufficient and well-controlled research evidence for this product, so use it with caution. There is a small amount of trazodone hydrochloride and its metabolites in breast milk, so lactating women should use it with caution. [Drug Use in Children] For patients under 18 years old, the effectiveness and safety of trazodone hydrochloride have not been determined, so it is not recommended. [Drug Use in the Elderly] This product has fewer side effects on the heart and very weak peripheral anticholinergic effects, so it is more suitable for elderly patients. |
