In Tg(+) mice, physostigmine (Eserine; 0.03-0.3 mg/kg; subcutaneous injection; administered daily for 6 weeks) can ameliorate cued memory deficits and contextual memory impairments [2]. At doses ≥0.2 mg/kg, physostigmine (intravenous; 0.1, 0.2 mg/kg) postpones the awakening of male Sprague-Dawley rats from isoflurane anesthesia [4].

Animal/Disease Models: Heterozygous transgenic mice (Tg(+) mice) [2]
Doses: 0.03, 0.1 and 0.3 mg/kg
Route of Administration: SC; one time/day for 6 weeks
Experimental Results: Tg(+) Animal Situation Memory deficits normalized, causing them to become more similar to Tg(-) animals.

Absorption, Distribution and Excretion
Physostigmine is readily absorbed by the gastrointestinal tract, subcutaneous tissue, and mucous membranes. Renal excretion plays only a minor role in its clearance. Physostigmine is a tertiary amine, unlike quaternary ammonium anticholinesterase drugs, and can cross the blood-brain barrier. /Acetylcholinesterase/ Easily penetrates the blood-brain barrier. Time to peak effect: within 5 minutes after intravenous injection; Duration of effect: approximately 1 to 2 hours after intravenous injection. Very small amounts are excreted in urine; most are destroyed in the body through hydrolysis. Metabolism/Metabolites Easily hydrolyzed by cholinesterase. Physostigmine is largely destroyed in the body, primarily through the hydrolysis of ester bonds by plasma esterases. In humans, a 1 mg dose… is largely destroyed within 2 hours after subcutaneous injection. Physostigmine binds to enzymes at ester bond sites to generate inactive methylcarbamoylase.
Easily hydrolyzed by cholinesterase.

Effects During Pregnancy and Lactation
◉ Overview of Drug Use During Lactation There is currently no information available regarding the use of physostigmine during lactation. ◉ Effects on Breastfed Infants As of the revision date, no relevant published information was found. ◉ Effects on Lactation and Breast Milk As of the revision date, no relevant published information was found regarding lactating women. In animal studies, cholinergic drugs increased oxytocin release, while physostigmine increased serum prolactin levels in humans. For mothers who have established lactation, prolactin levels may not affect their ability to breastfeed. Interactions The effects of anticholinesterase drugs on autonomic effector cells and the cortical and subcortical regions of the central nervous system (where receptors are primarily muscarinic) can be blocked by atropine. /Anticholinesterase Drugs/
The effects of anticholinesterase drugs on skeletal muscle can be enhanced by adrenaline or ephedrine…and blocked by D-tubocurarine. /Anticholinesterase Agents/
Sufficient amounts of…physostigmine…can prevent the alkyl phosphorylation of acetylcholinesterase by diisopropyl fluorophosphate. Short-acting drugs occupying the active site of cholinesterase can prevent…the alkyl phosphorylation of acetylcholinesterase by organophosphate compounds…this has been confirmed in both in vitro and in vivo experiments.
Administering physostigmine 15 minutes before administration reduces its toxicity in mice. Pyridoxime mesylate also causes mild redness.
For more complete data on interactions of physostigmine (9 in total), please visit the HSDB records page.

[1]. Pharmakotherapie--physostigmin post OP [Pharmacotherapy--physostigmine administered post-operatively]. Anasthesiol Intensivmed Notfallmed Schmerzther. 2007;42(3):188‐189.

[2]. Dong H, et al, Bertchume A, Vallera D, Csernansky JG. Acetylcholinesterase inhibitors ameliorate behavioral deficits in the Tg2576 mouse model of Alzheimer's disease. Psychopharmacology (Berl). 2005;181(1):145‐152.

[3]. Frascogna N. Physostigmine: is there a role for this antidote in pediatric poisonings? Curr Opin Pediatr. 2007;19(2):201‐205.

[4]. Physostigmine and Methylphenidate Induce Distinct Arousal States During Isoflurane General Anesthesia in Rats. Anesth Analg. 2016 Nov;123(5):1210-1219.

Physostigmine is a white, odorless, microCrystal powder. It is used as a cholinergic (anticholinesterase) drug and in veterinary medicine. (EPA, 1998) Physostigmine is a carbamate and indole alkaloid. It has a miotic effect, is an EC 3.1.1.8 (cholinesterase) inhibitor, and is also an antidote for curare poisoning. It is a cholinesterase inhibitor that is rapidly absorbed through cell membranes. It can be applied topically to the conjunctiva. It can also cross the blood-brain barrier for use in situations requiring central nervous system action, such as the treatment of severe anticholinergic poisoning. Physostigmine has been reported in Streptomyces, physostigmine, and other organisms with relevant data. See also: Physostigmine salicylate (in salt form). Drug Indications For the treatment of glaucoma and severe anticholinergic poisoning. Mechanism of Action Physostigmine inhibits acetylcholinesterase, the enzyme responsible for breaking down utilized acetylcholine. Physostigmine indirectly stimulates nicotinic and muscarinic receptors by interfering with acetylcholine metabolism, thereby increasing the availability of acetylcholine at the synapse. The characteristic pharmacological action of anticholinesterase drugs is primarily attributed to their inhibition of the hydrolysis of acetylcholine by acetylcholinesterase at the cholinergic transmission site. Therefore, neurotransmitter accumulation occurs, enhancing the effect of acetylcholine released by cholinergic impulses or leaking from nerve endings. /Acetylcholine/ …Physostigmine is a tertiary amine whose effect is /minimally/unrelated to acetylcholinesterase inhibition. However, at sufficiently high doses, it has a direct blocking effect on autonomic ganglia.
In chronic open-angle glaucoma, the exact mechanism by which miotics lower intraocular pressure is not fully understood; however, contraction of the ciliary muscle clearly opens the seminiferous tubules, promoting aqueous humor outflow.
It increases the concentration of acetylcholine at cholinergic transmission sites by inhibiting the destruction of acetylcholine by acetylcholinesterase, antagonizing the effects of anticholinergic drugs that block postsynaptic acetylcholine receptors.
Therapeutic Uses

Antidote; Cholinesterase inhibitor; Miotic; Parasympathomimetic drug
Antidotes are valuable in the treatment of primary glaucoma and certain types of secondary glaucoma (e.g., retinopathy of prematurity after cataract extraction); congenital glaucoma is rarely effective with treatments other than surgery. Primary glaucoma is further divided into narrow-angle (acute congestive) and wide-angle (chronic simple) glaucoma…Antidotes lower intraocular pressure in both types of glaucoma by reducing resistance to aqueous humor outflow. ...In acute congestive glaucoma...mydriasis can be achieved with pilocarpine. Instill 1 to 2 drops of 2% or 4% pilocarpine nitrate every 10 to 15 minutes for 1 hour; thereafter, administer every 2 to 3 hours. Some ophthalmologists may use pilocarpine in combination with physostigmine salicylate. For chronic wide-angle glaucoma and secondary glaucoma, careful consideration of the individual patient's needs is necessary when choosing medications or combinations...available medications include...short-acting anticholinesterase agents (e.g., physostigmine salicylate, 0.25% and 0.5%)...physostigmine salicylate/
Compared to the use of potent, long-acting anticholinesterase agents for glaucoma treatment, pilocarpine alone (4%) or in combination with physostigmine salicylate (0.2%), 1-5 times daily, has not been found to cause a higher incidence of spontaneous lens opacity than in untreated patients of the same age.
Intravenous physostigmine can reverse many peripheral and central effects of atropine and related antimuscarinic drugs. Physostigmine salicylate can be used to reverse central anticholinergic syndrome caused by overdose or adverse reactions to these drugs. The initial intravenous or intramuscular dose is 2 mg, which may be increased if necessary.
For more complete data on the therapeutic uses of physostigmine (20 in total), please visit the HSDB record page.

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Drug Warnings
Physostigmine often causes conjunctival congestion. …Due to the frequent occurrence of conjunctivitis and allergic reactions, it is rarely tolerated for long periods.Prolonged use may lead to conjunctival follicle formation. Prolonged use of physostigmine ointment may cause pigmentation of the eyelid margins.
Conjunctival instillation solution…If measures are not taken (e.g., applying pressure to the inner canthus) to prevent absorption of the drug through the nasal mucosa, systemic reactions may occur.
…Contraindicated in patients with asthma. It should not be used in combination with cholinesterase drugs except for ophthalmic uses. /Neostigmine/
Veterinary Use: Its laxative effect in cattle usually causes pain. ...Contraindicated in...immobile intestinal obstruction, heart or lung disease, and older animals.
For more drug warnings (complete) data on physostigmine (12 of them), please visit the HSDB record page.

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Pharmacodynamics
Physostigmine is a parasympathomimetic drug, specifically a reversible cholinesterase inhibitor that effectively increases acetylcholine concentrations at cholinergic transmission sites. Physostigmine is used to treat glaucoma. Because it can cross the blood-brain barrier, it is also used to treat central nervous system symptoms caused by atropine overdose and other anticholinergic drug overdose. Physostigmine can reverse central and peripheral anticholinergic effects.

C15H21N3O2

275.34614

275.163

57-47-6

Physostigmine salicylate;57-64-7;Physostigmine hemisulfate;64-47-1;Physostigmine-d3;1217704-11-4

5983

Brown to black solid powder

1.2±0.1 g/cm3

422.3±55.0 °C at 760 mmHg

102-104 °C(lit.)

209.2±31.5 °C

0.0±1.1 mmHg at 25°C

1.616

1.89

1

4

2

20

403

2

C[C@@]12CCN([C@@H]1N(C3=C2C=C(C=C3)OC(=O)NC)C)C

PIJVFDBKTWXHHD-HIFRSBDPSA-N

InChI=1S/C15H21N3O2/c1-15-7-8-17(3)13(15)18(4)12-6-5-10(9-11(12)15)20-14(19)16-2/h5-6,9,13H,7-8H2,1-4H3,(H,16,19)/t13-,15+/m1/s1

(3aS,8aR)-1,3a,8-trimethyl-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indol-5-yl methylcarbamate

Physostigmine Eserine Antilirium Physostol Esromiotin Ezerin

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~50 mg/mL (~181.59 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (9.08 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 + to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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 (Please use freshly prepared in vivo formulations for optimal results.)