アナバシン

Acute exposure to cholinesterase inhibitors can cause a cholinergic crisis characterized by severe nausea/vomiting, salivation, sweating, bradycardia, hypotension, collapse, and convulsions. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved. Accumulation of ACh at motor nerves causes overstimulation of nicotinic expression at the neuromuscular junction. When this occurs symptoms such as muscle weakness, fatigue, muscle cramps, fasciculation, and paralysis can be seen. When there is an accumulation of ACh at autonomic ganglia this causes overstimulation of nicotinic expression in the sympathetic system. Symptoms associated with this are hypertension, and hypoglycemia. Overstimulation of nicotinic acetylcholine receptors in the central nervous system, due to accumulation of ACh, results in anxiety, headache, convulsions, ataxia, depression of respiration and circulation, tremor, general weakness, and potentially coma. When there is expression of muscarinic overstimulation due to excess acetylcholine at muscarinic acetylcholine receptors symptoms of visual disturbances, tightness in chest, wheezing due to bronchoconstriction, increased bronchial secretions, increased salivation, lacrimation, sweating, peristalsis, and urination can occur. Certain reproductive effects in fertility, growth, and development for males and females have been linked specifically to organophosphate pesticide exposure. Most of the research on reproductive effects has been conducted on farmers working with pesticides and insecticdes in rural areas. In females menstrual cycle disturbances, longer pregnancies, spontaneous abortions, stillbirths, and some developmental effects in offspring have been linked to organophosphate pesticide exposure. Prenatal exposure has been linked to impaired fetal growth and development. Neurotoxic effects have also been linked to poisoning with OP pesticides causing four neurotoxic effects in humans: cholinergic syndrome, intermediate syndrome, organophosphate-induced delayed polyneuropathy (OPIDP), and chronic organophosphate-induced neuropsychiatric disorder (COPIND). These syndromes result after acute and chronic exposure to OP pesticides.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 80(SRC), determined from a log Kow of 0.97(2) and a regression-derived equation(3), suggests that anabasine is expected to have high mobility in soil(SRC). However, anabasine has a pKa of 11.0(4), which indicates that this compound will exist in the protonated form at environmental pH values, and cations adsorb more strongly to soils than neutral molecules. Therefore, the mobility of anabasine is expected to be much lower than predicted(SRC). Volatilization of anabasine from moist soil surfaces will not an important fate process(SRC) as it will exist in the protonated form in the environment and the protonated form will not volatilize(SRC). Anabasine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 6.6X10-3 mm Hg(SRC), determined from a fragment constant method(5).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 80(SRC), determined from a log Kow of 0.97(2) and a regression-derived equation(3), indicates that anabasine is not expected to adsorb to suspended solids and sediment(SRC). A pKa of 11.0(4) indicates anabasine will exist entirely in the ionized form at pH values of 5 to 9 and therefore volatilization from water surfaces is not expected to be an important fate process. According to a classification scheme(5), an estimated BCF of 3(SRC), from its log Kow(2) and a regression-derived equation(6), suggests the potential for bioconcentration in aquatic organisms is low(SRC).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), anabasine, which has an estimated vapor pressure of 6.6X10-3 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase anabasine is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 4 hours(SRC), calculated from its rate constant of 1.0X10-10 cu cm/molecule-sec at 25 °C(SRC) determined using a structure estimation method(3).

Anabasine is a cholinesterase or acetylcholinesterase (AChE) inhibitor. A cholinesterase inhibitor (or 'anticholinesterase') suppresses the action of acetylcholinesterase. Because of its essential function, chemicals that interfere with the action of acetylcholinesterase are potent neurotoxins, causing excessive salivation and eye-watering in low doses, followed by muscle spasms and ultimately death. Nerve gases and many substances used in insecticides have been shown to act by binding a serine in the active site of acetylcholine esterase, inhibiting the enzyme completely. Acetylcholine esterase breaks down the neurotransmitter acetylcholine, which is released at nerve and muscle junctions, in order to allow the muscle or organ to relax. The result of acetylcholine esterase inhibition is that acetylcholine builds up and continues to act so that any nerve impulses are continually transmitted and muscle contractions do not stop. Among the most common acetylcholinesterase inhibitors are phosphorus-based compounds, which are designed to bind to the active site of the enzyme. The structural requirements are a phosphorus atom bearing two lipophilic groups, a leaving group (such as a halide or thiocyanate), and a terminal oxygen.

Anabasine produces symptoms similar to nicotine poisoning, such as nausea, abdominal pain, vomiting, diarrhea, diaphoresis, flushing, dizziness, disturbed hearing and vision, confusion, weakness, palpitations, altered respiration and hypotension. (L327)

The Koc of anabasine is estimated as 80(SRC), using a measured log Kow of 0.97(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that anabasine is expected to have high mobility in soil. However, the pKa of anabasine is 11.00(4), which indicates that this compound will exist in the protonated form under environmental pH values and cations adsorb more strongly to soil surfaces than neutral molecules (SRC).

IN ANABASIS APHYLLA L, CHENOPODIACEAE...IN NICOTIANA GLAUCA GRAHAM, SOLANACEAE...

Anabasine is the principal alkaloid of Anabasis aphylla, present at 1-2% in the shoots, and is also found to about 1% in Nicotiana glauca(1).

SYMPTOMATOLOGY: 1. BURNING SENSATION IN MOUTH & THROAT, SALIVATION, NAUSEA, ABDOMINAL PAIN, VOMITING, DIARRHEA. GI REACTIONS ARE LESS SEVERE BUT DO OCCUR AFTER CUTANEOUS & RESP EXPOSURES. /NICOTINE/

SYMPTOMATOLOGY: 2. SYSTEMIC EFFECTS INCL HEADACHE, SWEATING, DIZZINESS, AUDITORY & VISUAL DISTURBANCES, CONFUSION, WEAKNESS, & INCOORDINATION. 3. AT FIRST RESP...DEEP & RAPID, BLOOD PRESSURE...HIGH...PULSE...SLOW. INTENSE VAGAL STIMULATION MAY CAUSE TRANSIENT CARDIAC STANDSTILL OR PAROXYSMAL ATRIAL FIBRILLATION. PUPILS ARE GENERALLY CONSTRICTED. /NICOTINE/

SYMPTOMATOLOGY: 4. CENTRAL NERVOUS EXCITATION...EVIDENCED BY TREMORS & SOMETIMES BY CLONIC-TONIC CONVULSIONS. 5. AS DEPRESSION DEVELOPS, PUPILS DILATE, BLOOD PRESSURE FALLS AND PULSE BECOMES RAPID & OFTEN IRREGULAR. FAINTNESS, PROSTRATION, CYANOSIS & DYSPNEA PROGRESS TO COLLAPSE. 6. DEATH FROM PARALYSIS OF RESPIRATORY MUSCLES. /NICOTINE/

A 29 YR OLD MAN USED THERAPEUTIC CLYSMA OF TAR FOR RECTAL PROLAPSE. HE EXPERIENCED SHARP GENERAL WEAKNESS, VERTIGO & NAUSEA. WHEN EXAM, HE WAS IN EXTREMELY CRITICAL CONDITION. CARDIOVASCULAR SIGNS WERE DISTURBED & THERE WAS ACROCYANOSIS & LOWERED BODY TEMP; PT WAS STILL CONSCIOUS. 35 MIN AFTER 1ST AID RESP BECAME SEVERLY DEPRESSED & HE BECAME UNCONSCIOUS. THERE WAS MARKED CYANOSIS. URINATION WAS FREQUENT & PAINLESS. ANALYSIS OF URINE & STOMACH CONTENTS DEMONSTRATED ALKALOID ANABASINE. NO SEQUELAE APPEARED ON LATER FOLLOW UP.

Acute & subacute toxicity: increased salivation, vertigo, confusion, disturbed vision & hearing, photophobia, cold extremities, nausea, vomiting, diarrhea, syncope, colonic spasms.

Extracted on a large scale in Russia. Industrial extraction processes: Sadykov, Timbekov; J Appl Chem USSR 29: 148 (1956).

Derivation: (1) Extraction from Anabasis aphylla and Nicotiana glauca, (2) synthetic

Neo-nicotine is a name given to a synthetic anabasine (the DL isomer) produced and tested in the US by the Department of Agriculture.

ANABASINE WAS FIRST DESCRIBED BY AP OREKHOV IN 1929 IN THE PLANT ANABASIS APHYLLA WHICH GROWS IN LARGE QUANTITIES IN CENTRAL ASIA. FOR USE IN AGRICULTURE A 40% AQUEOUS SOLUTION OF THE SULFATES OF THE TOTAL ALKALOIDS OF ANABASIS IS PUT OUT. THE TOTAL ALKALOIDS CONTAIN 70% OF ANABASINE & 30% OTHER ALKALOIDS. IT IS PRACTICALLY EQUAL TO NICOTINE IN INSECTICIDAL ACTIVITY.

Anabasine...is the principal alkaloid of Anabasis aphylla, present at 1-2% in the shoots, and is also found to about 1% in Nicotiana glauca.