Topic 3: nicotine Flashcards
treats
asthma, cough, toothache, sedative
scorpion stings
snakebites
genus
Nicotiana, named after Jean Nicot fresh ambassador to Portugal
native to
SA
Columbus
Cuba 1492
natives drinking smoke
who popularized tobacco smoking in Elizabethan England
John Hawkins, Frances Drake, Walter Raleigh
most tobacco used today is from
Nicotinana tabacum
John Rolfe
cultivate N. rustica in Virginia, 17th cent. doesn't compete with tabacum virginia tabacco (N. tabacum)
Nicotine as insecticide
WW2
waste from tobacco industry
family
Slanaceae
“herbs of consolation”
nicotine
major alkaloid, pyrrolidine , presence of ring structure containing N synthesized in root stored in leaf one of the most toxic drugs ever known acts almost as fast as cyanide most addictive drug in widespread use
M. sexta
tobacco specialist
tobacco hornworm grows slow on high nicotine diets
Posset and Remagnet
isolated/structure of nicotine
nicotine composition
pyridine + N-methylpyrrolidine ring
- Nicotinate
- nicotinic acid/Vitamin B3/niacin (essential for E metabolism and DNA repair), water soluble vitamin
- nicotine synthase activity
Nornicotine
undesired
precursor for carcinogen
detected in urine
Synthesis
condensation of an intermediate in the NAD salvage pathway and the methylpyrrolinium cation form ornithine via putrescine
physiology effects (diseases)
lung cancer, coronary disease, emphysema of the lungs
physiology
stimulant, represent, tranq.
analgesic
causes release of adrenaline from adrenal glands
activates reward pathway -> addiction!
lethal dose
60mg/kg
low nicotine effects
increase BP, HR
nausea, weakness, dizziness
high nicotine effects
convulsions
paralysis
suffocation
blocks cholinergic channels
affects
CNS and ANS (PNS)
ANS effects
mimics acetylcholine
CNS effects
increased arousal
nAChR
ligand gated ion channel
neuromuscular junction
nicotine introduced to system
binds to nAChR
agonist
and eventually antagonist
Cholinergic system in insects vs mammals
limited to CNS
both CNS and PNS
metabolism and elimination
deactivated in liver
effects hypothalamus, leads to release of ADH, preventing elimination from kidneys
liver metabolism
number of metabolites most import. is cotinine 80%. 2 steps: 1. by cytochrome P450 - produce nicotine imodium salt 2. catalysed by aldehyde oxidase (AOX)
another is Nicotine N’oxide (NNO) 7%
3HC
main nicotine metabolite detected in urine
3HC-Gluc
40-60% of nicotine dose in urine
CNO
reduced back to NNO in vivo
plant consumption and performance of M. seat larvae were _______ correlated with constitutive levels in nicotine lab feeding trials
negatively
only IRpmt plants had
strongly reduced nicotine content
low nicotine lines…
more likely to be fed on
low nicotine line
phenotype caused by synergistic effect of loci: nic1 and nic2
acetylaldehyde
increases reward properties of nicotine
also in tobacco smoke
age related effect (younger animals had more sensitivity)
M. sexta prefer and grew faster on
IRpmt than WT strains
diff between WT and IRpmt lines?
dramatic reduction of MeJA elicited and constitutive nicotine production
increase in antabine content
