From Biohack

http://en.wikipedia.org/wiki/Physostigmine

Physostigmine (also known as eserine from éséré, West African name for the Calabar bean) is a parasympathomimetic, specifically, a reversible cholinesterase inhibitor obtained from the Calabar bean. It can also be obtained from Streptomyces griseofuscus. By interfering with the metabolism of acetylcholine, physostigmine indirectly stimulates both nicotinic and muscarinic receptors. The chemical was synthesized for the first time in 1935 by the chemists Percy Lavon Julian and Josef Pikl.

Possible side effects include depression, and overdose can cause a cholinergic syndrome. It is available in the U.S. under the trade names Antilirium, Eserine Salicylate, Isopto Eserine, and Eserine Sulfate. Physostigmine is also used in creating opiates, discovered by Ludwig Laqueur.

A similar stimulation of the non-striped muscle in the alimentary canal results in violent vomiting and purging, if a large dose has been taken. Physostigmine, indeed, stimulates nearly all the non-striped muscles in the body, and this action upon the muscular coats of the arteries, and especially of the arterioles, causes a great rise in blood-pressure shortly after its absorption, which is very rapid. The terminals of the vagus nerve are also stimulated, causing the heart to beat more slowly. Later in its action, the drug depresses the intra-cardiac motor ganglia, causing prolongation of diastole and finally arrest of the heart in dilatation. A large lethal dose kills by this action, but the minimum lethal dose by its combined action on the respiration and the heart. The respiration is at first accelerated by a dose of physostigmine, but is afterwards slowed and ultimately arrested. The initial hastening is due to a stimulation of the vagus terminals in the lung, as it does not occur if these nerves are previously divided. The final arrest is due to paralysis of the respiratory centre in the medulla oblongata, hastened by a quasi-asthmatic contraction of the non-striped muscular tissue in the bronchial tubes, and by a "water-logging" of the lungs due to an increase in the amount of bronchial secretion. It may here be stated that the non-striped muscular tissue of the bladder, the uterus and the spleen is also stimulated, as well as that of the iris. It is only in very large doses that the voluntary muscles are poisoned, there being induced in them a tremor which may simulate ordinary convulsions. The action is a direct one upon the muscular tissue (cf. the case of the gland-cells), since it occurs in an animal whose motor nerves have been paralyzed by curare. Consciousness is entirely unaffected by physostigmine, there being apparently no action on any part of the brain above the medulla oblongata.

But the influence of the alkaloid upon the spinal cord is very marked and characteristic. The reflex functions of the cord are entirely abolished, and it has been experimentally shown that this is due to a direct influence upon the cells in the anterior cornua. It is precisely the reverse of the typical action of strychnine. Near the termination of a fatal case there is a paralysis of the sensory columns of the cord, so that general sensibility is lowered. The alkaloid calabarine is, on the other hand, a stimulant of the motor and reflex functions of the cord, so that only the pure alkaloid physostigmine and not any preparation of Calabar bean itself should be used when it is desired to obtain this action. Besides the secretions already mentioned as being stimulated, the bile, the tears and the perspiration are increased by the exhibition of this drug.

Whether administered in the form of the official lamella or by subcutaneous injection, physostigmine causes a contraction of the pupil more marked than in the case of any other known drug. That this action is a direct and not a nervous one is shown by the fact that if the eye be suddenly shaded the pupil will dilate a little, showing that the nerves which cause dilatation are still competent after the administration of physostigmine. Besides the sphincter pupillae, the fibers of the ciliary muscle are stimulated. There is consequently spasm of accommodation, so that clear vision of distant objects becomes impossible. The intra-ocular tension is markedly lowered. This action, at first sight somewhat obscure, is due to the extreme pupillary contraction which removes the mass of the iris from pressing upon the spaces of Fontana, through which the intraocular fluids normally make a very slow escape from the eye into its efferent lymphatics.

Hmm? Cholinergic hyperactivity and negative symptoms: behavioral effects of physostigmine in normal controls.

Schizophr Res. 1993 Mar;9(1):19-23.

Cholinergic hyperactivity and negative symptoms: behavioral effects of physostigmine in normal controls.

Tandon R, Greden JF, Haskett RF.

Department of Psychiatry, University of Michigan Medical Center, Ann Arbor 48109.

Intravenous infusion of physostigmine (a centrally active anticholinesterase agent) in normal subjects leads to a syndrome of psychomotor inhibition; this has been proposed as a model for selected symptoms of depression. In view of its similarity to the negative schizophrenic syndrome, we compared the 'physostigmine syndrome' to the negative symptom profile by evaluating the behavioral effects of intravenous physostigmine infusion in seven normal volunteers. Observer ratings and self description revealed significant withdrawal, apathy, alogia, lethargy, decreased energy, slowed thoughts, diminished affective responsivity, and reduced hedonic capacity. Subjects did not report sadness, ideas of hopelessness, worthlessness, or guilt. These findings support the implication of cholinergic hyperactivity as one mechanism in the pathophysiology of negative schizophrenic sympto

Extraneous memantine ref with mention of physostigmine

Memantine: The Next Trend in Academic Performance Enhancement?

The drug acts by noncompetitively binding to the N-methyl D-aspartate (NMDA) receptors of neurons in brain tissue 'to prevent overstimulation by glutamate.2 When this excitatory neurotransmitter overactivates NMDA receptors in a tonic manner, an excessive influx of neurotoxic calcium ions follows.2 The resultant excitotoxicity may play a role in the impairment of memory and cognition in AD.3 Because memantine has a low-to-moderate affinity for NMDA receptors, it does not seem to block normal glutamate transmission; rather, it reduces abnormal neurotransmitter-mediated activation of the receptors,4 thereby potentially reducing excitotoxic neuronal damage. This form of neuroprotection may explain the improved cognition in patients with AD reported in the literature.5–7 Can transient low-level, nonpathologic, glutamate-mediated neuronal damage occur in the brains of normal individuals? And, if so, could memantine's neuroprotective effect antagonize the damaging effects and enhance memory potential in these individuals? Future research should address these issues. Memantine's suggested neuroprotective effect2,8 may also increase brain levels of the neuronal marker, N-acetyl aspartate (NAA). Because NAA is found primarily on neuronal axons in the brain,9 perhaps the neuroprotective effect of memantine can be measured by quantifying the change in NAA concentrations in brain tissue via magnetic resonance spectroscopy. Magnetic resonance spectroscopy has demonstrated that patients with AD show a decline in NAA relative to normal controls.10 The reduction in excitotoxicity via memantine's mechanism of action may allow affected neurons to regain some level of physiologic functioning, such as growth of neuronal processes and synaptogenesis, which is fundamental to learning and memory formation11—a process that is damaged in AD.2 Moreover, a direct relationship has been observed between NAA levels in the brain and intelligence. Healthy individuals with high levels of NAA appear to have higher scores on intelligence tests than healthy individuals with lower levels of this marker in brain tissue.12 It may be possible that the higher levels of NAA indicate an increased presence of neuronal processes and their synapses. The effects of drugs that have cognitive-enhancing potential have been studied in healthy individuals. Acetylcholinesterase inhibitors (some of which are used to treat AD), such as donepezil, huperzine , and physostigmine, have been shown to improve memory and cognitive tasks in normal subjects.13–15 Another medication that enhances cognitive performance is methylphenidate, a drug commonly prescribed for attention deficit hyperactivity disorder (ADHD) but increasingly used by healthy university students nationwide as an academic performance–enhancing agent.16 A recent national survey17 reported that ADHD medications have much higher rates of abuse in colleges with higher admission standards. Could memantine be misused by students for academic performance-enhancement in the near future?