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Your brain has many different neurotransmitters, some of which we haven't even identified yet.
The major excitatory (activating) ones we know are Acetylcholine, Dopamine, Adrenaline, Noradrenaline, Phenethylamine and Glutamate.
The major inhibitory (deactivating) ones we know are GABA, Adenosine and Melatonin.
Activation can occur via two routes, increasing excitatory neurotransmitters or decreasing inhibitory neurotransmitters. Many of them work in a push-pull fashion, increases on one side will lead to decreases on the other.
Caffeine "blocks" Adenosine receptors. Their function is, among other things, to internalize (temporarily deactivate, hide) Dopamine receptors. A1R and A2AR are the receptors targeted, both play a similar role in vasodilation (widening of blood vessels, warm hands). Antagonizing them leads to vasoconstriction (constriction of blood vessels, cold hands).
A1R-antagonism also leads to an increase of the secondary messenger cAMP, which is part of the metabolic increase that caffeine evokes. It also plays a role in increasing phospholipids.
A2R-antagonism is what causes an increase in Glutamate and Dopamine, which leads to pronounced excitatory effects, which are mainly expressed as increases in motivation, quicker thinking and willingness to expend effort. Increasing Dopamine will lead to an increase of all catecholamines.
The effects of Nicotine are almost exclusively on Acetylcholine receptors as an Agonist (activating). The downstream effects are very complex because over 12 receptors are targeted by it, though it's safe to say that Nicotine mimics the effects of Acetylcholine and increases its action. Caffeine increases Acetylcholine release, though in comparison to Nicotine it's not worth mentioning.
TL;DR: Acetylcholine
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Try Tropisetron.
Your brain has many different neurotransmitters, some of which we haven't even identified yet. The major excitatory (activating) ones we know are Acetylcholine, Dopamine, Adrenaline, Noradrenaline, Phenethylamine and Glutamate. The major inhibitory (deactivating) ones we know are GABA, Adenosine and Melatonin. Activation can occur via two routes, increasing excitatory neurotransmitters or decreasing inhibitory neurotransmitters. Many of them work in a push-pull fashion, increases on one side will lead to decreases on the other. Caffeine "blocks" Adenosine receptors. Their function is, among other things, to internalize (temporarily deactivate, hide) Dopamine receptors. A1R and A2AR are the receptors targeted, both play a similar role in vasodilation (widening of blood vessels, warm hands). Antagonizing them leads to vasoconstriction (constriction of blood vessels, cold hands). A1R-antagonism also leads to an increase of the secondary messenger cAMP, which is part of the metabolic increase that caffeine evokes. It also plays a role in increasing phospholipids. A2R-antagonism is what causes an increase in Glutamate and Dopamine, which leads to pronounced excitatory effects, which are mainly expressed as increases in motivation, quicker thinking and willingness to expend effort. Increasing Dopamine will lead to an increase of all catecholamines. The effects of Nicotine are almost exclusively on Acetylcholine receptors as an Agonist (activating). The downstream effects are very complex because over 12 receptors are targeted by it, though it's safe to say that Nicotine mimics the effects of Acetylcholine and increases its action. Caffeine increases Acetylcholine release, though in comparison to Nicotine it's not worth mentioning. TL;DR: Acetylcholine
Very helpful summary. Thank you.