Lobeline

Description

Lobeline is mainly present in Lobelia chinensis, Lobelia inflata, Campanula medium, Lobelia hassleri, and Lobelia nicotianaefolia . Lobelia inflata has also been considered as an Indian tobacco and has been used for the treatment of respiratory diseases for a long history. It was also a treatment of asthma by American Aborigines. In the United States during the nineteenth century, doctors use Lobelia inflata as a vomiting agent, to remove the poison from the body. It is also called “vomit grass.” Now Lobelia inflata is still used to clear throat, bronchial, lung, and other respiratory mucus .

Chemical Properties

Crystalline solid; melts at 130°C (266°F);slightly soluble in water, dissolves readily inhot alcohol, ether, chloroform, and benzene.

Physical properties

Appearance: White crystalline or granular powder, odorless, and bitter. Solubility: Soluble in ethanol or chloroform, slightly soluble in water. Melting point: 130–131?°C.

History

In the 1930s, the chemical synthesis process of lobeline was completed, and its artificial synthesis was realized, which was found in Lobelia inflata from the North American Campanulaceae. It was commonly used as a lobeline hydrochloride. Because of its structure similar to nicotine, it was initially used for the treatment of respiratory diseases. Further study found that lobeline can selectively excite the carotid sinus peripheral chemoreceptors, then reflect the excitement of the medullary breathing center, and enhance respiratory function. Therefore, it is widely used as a respiratory stimulant .
Although lobeline showed similar biological activity with nicotine, its potency is just only 1/5~1/20 of nicotine. Hence, lobeline was used as a substitute for nicotine in many smoking cessation products. However, in 1993, the Food and Drug Administration (FDA) banned the sale of smoking cessation products containing lobeline because it was ineffective in helping people quit smoking. However, the research of lobeline in drug addiction still continues.

Uses

Lobeline is the principal lobelia alkaloid.It occurs in the seeds and herb of Indiantobacco (Lobelia inflata and Lobeliaceae). Itis used as a respiratory stimulant. Its sulfatesalt is used in antismoking tablets.

Uses

The action of lobeline is in many respects similar to nicotine; however, it is 50–100 times weaker than nicotine. It is also first, a stimulant, and second, a depressant of sympathetic ganglia, parasympathetic ganglia, adrenal glands, and others. It can be used as a drug to assist with quitting smoking.

Definition

ChEBI: An optically active piperidine alkaloid having a 2-oxo-2-phenylethyl substituent at the 2-position and a 2-hydroxy-2-phenylethyl group at the 6-position.

Indications

Lobeline was recorded in chemical drug and preparations as lobeline hydrochloride, which is prepared as injection for the treatment of central respiratory inhibition induced by a variety of reasons. In addition, it is also used for the treatment of neonatal stasis, carbon monoxide, opioid poisoning, and so on.

Health Hazard

The structure of lobeline is different fromthose of nicotine and anabasine. It does nothave a pyridine ring, similar to the lattertwo alkaloids. However, its pharmacologicaction is similar to but less potent than thatof nicotine. Like anabasine, it is a respiratorystimulant. The toxic symptoms includeincreased salivation, nausea, vomiting, diarrhea,and respiratory distress.

Pharmacology

The pharmacological effects of lobeline are extensive, mainly manifested as nicotine-like effect. On the one hand, lobeline can selectively excite the carotid sinus and aortic body chemoreceptors and induce reflective excitement of the respiratory center and vagus center. Lobeline showed better excitatory effect for the respiratory inhibition caused by morphine. There is bronchiectasis effect directly when lobeline is inhaled, hence, against pilocarpine and acetylcholine-induced tracheal contraction. When the dose increased, lobeline can directly stimulate the respiratory center and excite vagal center (reducing heart rate) and vomiting center in medulla oblongata. In addition, lobeline showed dual role in the regulation of ganglion, as manifested excitement and inhibition in chronological order. Lobeline has a zebra-like effect on the striated muscle. In addition, it also has a certain anticancer effect, as manifested by significantly inhibiting the uptake of oxygen in mouse ascites cancer cells .

Clinical Use

It is mainly used in the treatment of (1) neonatal asphyxia, (2) suffocation caused by carbon monoxide, (3) poisoning induced by inhalation of anesthetics and other central inhibitors (such as opioids and barbiturates), and (4) respiratory failure caused by pneumonia, diphtheria, and other infectious diseases.

Side effects

Lobeline also showed side effects, such as nausea, vomiting, cough, headache, palpitations, and other adverse reactions.

Synthesis

Lobeline, 1-methyl-2-(|?-hydroxy-|?-phenylethyl)-6-phenacylpiperidine (13.1.33), is the primary alkaloid of leaves from Lobelia inflata. It is synthesized by condensation of 2,6- dimethylpyridine with two moles of benzaldehyde, giving |á,|á??-distyrylpyridine (13.1.28) [37¨C39]. Exhaustive bromination of this product and subsequent dehydrobromination of the resulting tetrabromo derivative (13.1.29) leads to the formation of |á,|á??-diphenylethinylpyridine (13.1.30). Hydration of the triple bonds of the product (13.1.30) gives |á,|á??- diphenacylpyridine (13.1.31). Reacting this with methyl p-toluenesulfonate gives |á,|á??-diphenacylpyridinium N-methyl-p-toluenesulfonate (13.1.32), which is carefully reduced by hydrogen into the desired lobeline (13.1.33) using simultaneously palladium and platinum catalysts. The product is a racemic mixture from which the levorotatory isomer can be isolated if necessary

Raw materials

Preparation Products