Appetite suppressants (II): 5-hydroxytryptamine analogues

2. 5-hydroxytryptamine-like neurotransmitter drugs

Pharmacological effects: It mainly exerts its appetite-suppressing effect through the following pathways.

① It promotes the release of serotonin stored in nerve endings and stimulates the feeding center.

② It selectively inhibits the reuptake of serotonin, prolonging its effect and is related to synaptic receptors.

These drugs do not have a central nervous system stimulant effect, and prolonged treatment can maintain weight loss without causing dependence.

Commonly used medications:

(1) Fenfluramine is also known as trifluoromethyl-m-phenylpropylethylamine or fluorophenylpropylamine.

It is one of the most frequently used and reported new drugs in recent years, with high efficacy and few side effects, and it has now been domestically produced.

This drug can promote the release of serotonin from nerve endings, stimulate the satiety center in the hypothalamus, inhibit overeating caused by insulin and α-deoxyglucose, increase the dependence of peripheral tissues on insulin, and promote the uptake and utilization of glucose by muscle tissue.

This indirectly reduces the amount of glucose converted into fat in fat cells, which is an important factor that directly affects the distribution of energy reserves.

It can also significantly affect lipoprotein metabolism, reducing serum total cholesterol, triglycerides, low-density lipoprotein (LDL), and β-lipoprotein, increasing high-density lipoprotein (HDL) levels, and decreasing the LDL/HDL ratio, thus having an anti-atherosclerotic effect. It promotes the breakdown of fat by growth hormone, reducing weight, and also has a certain antihypertensive effect, enhancing the antihypertensive effects of antihypertensive drugs such as guanethidine, methyldopa, and reserpine, and has a certain hypoglycemic effect.

It has few side effects, no central nervous system stimulant effect, is not easily addictive or psychologically dependent, and does not cause significant damage to organs such as the heart, liver, and kidneys.

The main side effects include drowsiness, nausea, and vomiting. Some patients may experience depression after discontinuing the medication.

This drug is also suitable for obese patients with hypertension, coronary heart disease, diabetes, and hyperlipidemia.

Given the reports of depressive symptoms occurring after taking this medication, it is speculated that this may be due to drug-induced restlessness and agitation; therefore, it is contraindicated for patients with depression.

Drivers and workers at heights should use this product with caution.

The usual dose is 20 mg three times a day, which can be gradually increased to 120 mg per day.

(2) Fluoxetine, also known as Prozac or Prozac, is a new type of antidepressant.

Its daily dose can be as high as 20-60 mg, which can significantly reduce weight. It increases the number of serotonin binding to postsynaptic membrane receptors in the brain by blocking the reuptake of serotonin by the presynaptic membrane of serotonin neurons, thereby improving the function of serotonin.

It has few side effects, mainly symptoms of sympathetic nerve excitation, such as dizziness, dry mouth, as well as insomnia, agitation, diarrhea, nausea, and constipation, with minimal impact on the heart.

Its indications are similar to those of fenfluramine.

However, due to the high price of imported fluoxetine, it cannot be widely promoted.

Domestically produced fluoxetine is now available, which will bring good news to many patients.

(3) Other drugs, such as M-chlorophenylpieraione, are under investigation.

3. Choice of appetite suppressants: Currently, diethylamine benzophenone, chlorpheniramine, and fluphenazine are commonly used.

Diethylamine benzophenone has fewer side effects and is cheaper than other drugs. It has the same weight-reducing effect as chlorpheniramine maleate and can be used as a routine choice.

Sometimes it can be used in conjunction with chlorpheniramine or alternately with phenylbutazone.

Fenfluramine is more suitable for those who are particularly easily agitated or nervous, as well as obese patients with diabetes, hypertension, coronary heart disease, or hyperlipidemia.

For obesity caused by phenothiazines, fenfluramine may be the best treatment.

However, it should be avoided by people with depression.

(II) Oral hypoglycemic agents – Biguanides

1. Mechanism of action

(1) Suppress appetite and reduce weight.

(2) Reduce or delay the absorption of sugar in the gastrointestinal tract.

(3) Increased excretion of fat and other substances in feces, resulting in heat loss.

(4) It lowers the glucose permeation threshold of muscle cells, thereby increasing the oxidation of glucose in muscles.

(5) Reduce hyperinsulinemia during fasting or after meals.

This type of medication does not lower blood sugar in obese patients without diabetes, so obese patients without diabetes can also take it.

Under the same dietary control conditions, those who took this medication experienced a 20% greater weight loss than those who did not. This type of medication can help 80% to 90% of obese patients achieve weight loss.

According to reports, the average weight loss is 3 to 3.5 kilograms over 6 months.

However, prolonged treatment can actually weaken the therapeutic effect.

By week 12, weight loss may stop.

A treatment method involving 3 months of medication followed by a 2-month break can achieve satisfactory results.

2. Commonly Used Drugs and Their Usage

(1) Phenformin (Glucose-lowering agent), orally, starting with 50 mg twice a day, then increasing by 50 mg per week until gastrointestinal irritation symptoms occur or up to 300 mg/day.

(2) Metformin (hypoglycemic tablets), orally, starting with 500 mg twice a day, then increasing by 500 mg each week until gastrointestinal symptoms appear or the dose reaches 3000 mg/day.

3. Side effects and contraindications: Common side effects are as follows.

(1) Nausea, vomiting, loss of appetite and diarrhea are signs that the maintenance dose has been reached and will lessen or disappear during continued medication.

(2) Fatigue, weakness, and metallic taste in the mouth will disappear on their own after reducing the dosage or stopping the medication.

(3) Drug rash.

(4) It inhibits the absorption of vitamin B₁₂, certain amino acids and bile, which can easily lead to B₁₂ deficiency.

(5) It can easily induce lactic acidosis, which is more common in people with liver or kidney dysfunction.

(6) Sometimes hypoglycemia may occur, mainly manifested as sweating, weakness and dizziness. If it is severe, you can take a small amount of sugar water, but remember that this is for weight loss, so do not supplement too much.

Contraindications: Poor liver and kidney function can lead to very high plasma glucose concentrations, causing cellular hypoxia, increased lactic acid production, and accumulation.

Heart failure and impaired lung function lead to increased lactic acid production due to hypoxia.

Therefore, it is contraindicated in individuals with liver or kidney dysfunction or severe liver or kidney disease, heart failure, myocardial infarction, hypovolemic shock due to dehydration or blood loss, ethanol (alcohol) poisoning, or the elderly.