Pseudaconitine, also known as nepaline (C₃₆H₅₁NO₁₂), is an extremely toxic

alkaloid Alkaloids are a broad class of natural product, naturally occurring organic compounds that contain at least one nitrogen atom. Some synthetic compounds of similar structure may also be termed alkaloids. Alkaloids are produced by a large varie ...

found in high quantities in the

root In vascular plants, the roots are the plant organ, organs of a plant that are modified to provide anchorage for the plant and take in water and nutrients into the plant body, which allows plants to grow taller and faster. They are most often bel ...

s of '' Aconitum ferox'', also known as Indian Monkshood, which belongs to the family

Ranunculaceae Ranunculaceae (, buttercup or crowfoot family; Latin "little frog", from "frog") is a family (biology), family of over 2,000 known species of flowering plants in 43 genera, distributed worldwide. The largest genera are ''Ranunculus'' (600 spec ...

. The plant is found in East Asia, including the

Himalayas The Himalayas, or Himalaya ( ), is a mountain range in Asia, separating the plains of the Indian subcontinent from the Tibetan Plateau. The range has some of the Earth's highest peaks, including the highest, Mount Everest. More than list of h ...

History

Pseudaconitine was discovered in 1878 by Wright and Luff. They isolated a highly toxic

from the roots of the plant ''Aconitum ferox'' and called it pseudaconitine. The poison is also called ''bikh'', ''bish'', or ''nabee''.

Toxicity and mechanism

Pseudaconitine is a moderate

inhibitor Inhibitor or inhibition may refer to: Biology * Enzyme inhibitor, a substance that binds to an enzyme and decreases the enzyme's activity * Reuptake inhibitor, a substance that increases neurotransmission by blocking the reuptake of a neurotransmi ...

of the

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

acetylcholinesterase Acetylcholinesterase (HUGO Gene Nomenclature Committee, HGNC symbol ACHE; EC 3.1.1.7; systematic name acetylcholine acetylhydrolase), also known as AChE, AChase or acetylhydrolase, is the primary cholinesterase in the body. It is an enzyme th ...

. This enzyme breaks down the

neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a Chemical synapse, synapse. The cell receiving the signal, or target cell, may be another neuron, but could also be a gland or muscle cell. Neurotra ...

acetylcholine Acetylcholine (ACh) is an organic compound that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Par ...

through

hydrolysis Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution reaction, substitution, elimination reaction, elimination, and solvation reactions in which water ...

Inhibition Inhibitor or inhibition may refer to: Biology * Enzyme inhibitor, a substance that binds to an enzyme and decreases the enzyme's activity * Reuptake inhibitor, a substance that increases neurotransmission by blocking the reuptake of a neurotransm ...

of this enzyme causes a constant stimulation of the postsynaptic

membrane A membrane is a selective barrier; it allows some things to pass through but stops others. Such things may be molecules, ions, or other small particles. Membranes can be generally classified into synthetic membranes and biological membranes. Bi ...

by the neurotransmitter which it cannot cancel. This accumulation of acetylcholine may thus lead to the constant stimulation of the

muscles Muscle is a soft tissue, one of the four basic types of animal tissue. There are three types of muscle tissue in vertebrates: skeletal muscle, cardiac muscle, and smooth muscle. Muscle tissue gives skeletal muscles the ability to muscle contra ...

glands A gland is a Cell (biology), cell or an Organ (biology), organ in an animal's body that produces and secretes different substances that the organism needs, either into the bloodstream or into a body cavity or outer surface. A gland may also funct ...

and

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain, spinal cord and retina. The CNS is so named because the brain integrates the received information and coordinates and influences the activity o ...

. Furthermore, it appears the substance in small quantities also causes a tingling effect on the tongue, lips and skin.Cash, J.T., Dunstan, W.R., ''The Pharmacology of Pseudaconitine and Japaconitine considered in relation to that of Aconitine'', 1901

Structure and reactivity

Pseudaconitine is a diterpene alkaloid, with the chemical formula C₃₆H₅₁NO₁₂. The

crystal A crystal or crystalline solid is a solid material whose constituents (such as atoms, molecules, or ions) are arranged in a highly ordered microscopic structure, forming a crystal lattice that extends in all directions. In addition, macros ...

melts at 202 °C and is moderately soluble in water, but more so in alcohol. This shows that it is a

lipophilic Lipophilicity (from Greek language, Greek λίπος "fat" and :wikt:φίλος, φίλος "friendly") is the ability of a chemical compound to dissolve in fats, oils, lipids, and non-polar solvents such as hexane or toluene. Such compounds are c ...

substance. When heated in the dry state, it undergoes

pyrolysis Pyrolysis is a process involving the Bond cleavage, separation of covalent bonds in organic matter by thermal decomposition within an Chemically inert, inert environment without oxygen. Etymology The word ''pyrolysis'' is coined from the Gree ...

and pyropseudaconitine (C₃₄H₄₇O₁₀N) is formed. This does not have the same tingling effect as pseudaconitine.Tsudaan Y., Marion L., ''Pseudaconitine, and the stereochemical relationship of the highly oxygenated aconite alkaloids'', 1963

References

{{reflist Diterpene alkaloids Plant toxins Phenol ethers Acetate esters Benzoate esters Acetylcholinesterase inhibitors

History

Toxicity and mechanism

Structure and reactivity

See also

References