physostigmine heptyl: RN given for (3aS-cis)-isomer; structure given in first source; possible use in therapy of Alzheimer's disease [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]
| ID Source | ID |
|---|---|
| PubMed CID | 65872 |
| CHEMBL ID | 433041 |
| SCHEMBL ID | 195028 |
| MeSH ID | M0148911 |
| Synonym |
|---|
| heptastigmine |
| n-demethyl-n-heptylphysostigmine |
| eptastigminum [inn-latin] |
| eptastigmina [inn-spanish] |
| brn 4883778 |
| physostigmine heptyl |
| carbamic acid, heptyl-, 1,2,3,3a,8,8a-hexahydro-1,3a,8-trimethylpyrrolo(2,3-b)indol-5-yl ester, (3as-cis)- |
| (-)-heptylphysostigmine |
| eptastigmine [inn] |
| heptylphysostigmine |
| (3as,8ar)-1,3a,8-trimethyl-1h,2h,3h,3ah,8h,8ah-pyrrolo[2,3-b]indol-5-yl n-heptylcarbamate |
| chembl433041 , |
| bdbm10972 |
| eptastigmine |
| [(3ar,8bs)-3,4,8b-trimethyl-2,3a-dihydro-1h-pyrrolo[2,3-b]indol-7-yl] n-heptylcarbamate |
| 101246-68-8 |
| eptastigmina |
| unii-6pzz52d76q |
| 6pzz52d76q , |
| eptastigminum |
| eptastigmine [mi] |
| eptastigmine [mart.] |
| SCHEMBL195028 |
| RRGMXBQMCUKRLH-CTNGQTDRSA-N |
| Q27265299 |
| DTXSID801317905 |
| Excerpt | Reference | Relevance |
|---|---|---|
| " After a single dose, heptastigmine remained for a long time in plasma (the terminal half-life was about 12 h), distributed widely in tissues (the volume of distribution was about 61) and brain concentrations were very high (4-22 times those found in plasma)." | ( Pharmacokinetics of heptastigmine in rats. Baldi, A; Cerretani, D; Segre, G; Urso, R, ) | 0.13 |
| " A preliminary evaluation of its pharmacodynamic and pharmacokinetic profiles in the elderly has now been made in 6 healthy subjects (63-84 years of age) given 30 mg eptastigmine as a single oral dose." | ( Pharmacodynamics and pharmacokinetics of eptastigmine in elderly subjects. Auteri, A; Imbimbo, BP; Lattuada, N; Luzzana, M; Mosca, A; Radice, D; Zecca, L, 1993) | 0.29 |
| " Drug interactions with cholinesterase inhibitors may occur by pharmacokinetic or pharmacodynamic mechanisms." | ( Pharmacokinetics and drug interactions of cholinesterase inhibitors administered in Alzheimer's disease. Crismon, ML, ) | 0.13 |
| " Pharmacodynamic activity of eptastigmine was evaluated with an assay of AChE activity in red blood cells." | ( Maximum tolerated dose and pharmacodynamics of eptastigmine in elderly healthy volunteers. Imbimbo, BP; Mant, T; Troetel, WM, 1998) | 0.3 |
| " Pharmacokinetic studies have revealed that after oral administration eptastigmine is rapidly distributed to the tissues and readily enters the CNS, where it can be expected to inhibit AChE for a prolonged period." | ( Eptastigmine: ten years of pharmacology, toxicology, pharmacokinetic, and clinical studies. Braida, D; Sala, M, 2001) | 0.31 |
| Excerpt | Reference | Relevance |
|---|---|---|
| "The ingestion of food significantly reduces the bioavailability of eptastigmine estimated by the assay of red blood cell acetylcholinesterase activity." | ( Effect of food on the absorption of eptastigmine. Bjornsson, TD; Imbimbo, BP; Troetel, WM, 1998) | 0.3 |
| Excerpt | Relevance | Reference |
|---|---|---|
| " The assay has been fully validated in the concentration range 50-2000 pg/ml and utilized for the analysis of clinical samples from subjects dosed with heptylphysostigmine." | ( Determination of picogram levels of heptylphysostigmine in human plasma using high-performance liquid chromatography with fluorescence detection. Constanzer, ML; Herold, ML; Matuszewski, BK, 1992) | 0.28 |
| "Transdermal delivery of cholinesterase inhibitors (ChEI) for treatment of dementia would have advantages associated with continuous dosing and enhanced compliance, but feasibility depends on achieving desired levels of central nervous system enzyme inhibition." | ( Transdermal patch delivery of acetylcholinesterase inhibitors. Becker, RE; Moriearty, PL; Thornton, SL, ) | 0.13 |
| " The reversal of scopolamine-induced impairment was characterized by the presence of an inverted U-shaped dose-response curve." | ( An inverted U-shaped curve for heptylphysostigmine on radial maze performance in rats: comparison with other cholinesterase inhibitors. Braida, D; Griffini, P; Lamperti, M; Maggi, A; Paladini, E; Sala, M, 1996) | 0.29 |
| " The relationship between patient performance and average steady-state AChE inhibition was described by an inverted U-shaped dose-response curve." | ( Eptastigmine: ten years of pharmacology, toxicology, pharmacokinetic, and clinical studies. Braida, D; Sala, M, 2001) | 0.31 |
| " Dose-response curves for tremor (central effect) and salivation (peripheral effect) showed that donepezil and icopezil possess a more favourable therapeutic index than the nonselective inhibitors, tacrine and heptylphysostigmine." | ( Pharmacology of selective acetylcholinesterase inhibitors: implications for use in Alzheimer's disease. Chapin, D; Hubbard, ST; Jones, SB; Liston, DR; Nason, D; Nielsen, JA; Ramirez, A; Shalaby, IA; Villalobos, A; White, WF, 2004) | 0.32 |
| Protein | Taxonomy | Measurement | Average | Min (ref.) | Avg (ref.) | Max (ref.) | Bioassay(s) |
|---|---|---|---|---|---|---|---|
| Cholinesterase | Homo sapiens (human) | IC50 (µMol) | 0.0135 | 0.0000 | 1.5599 | 10.0000 | AID1796572 |
| Acetylcholinesterase | Mus musculus (house mouse) | IC50 (µMol) | 0.1480 | 0.0007 | 1.1181 | 8.4000 | AID31789 |
| Acetylcholinesterase | Homo sapiens (human) | IC50 (µMol) | 0.0349 | 0.0000 | 0.9332 | 10.0000 | AID1796572; AID241692; AID262754; AID31163; AID31174; AID31176; AID511766; AID600978; AID600980 |
| Acetylcholinesterase | Homo sapiens (human) | Ki | 0.1000 | 0.0000 | 1.2786 | 9.7300 | AID1916837 |
| [prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023] | |||||||
| Assay ID | Title | Year | Journal | Article |
|---|---|---|---|---|
| AID130102 | Minimal dose to produce side effects was determined for diarrhea | 1994 | Journal of medicinal chemistry, Jun-24, Volume: 37, Issue:13 | Syntheses and anticholinesterase activity of tetrahydrobenzazepine carbamates. |
| AID262754 | Anticholinesterase activity against human erythrocyte AChE | 2006 | Journal of medicinal chemistry, Apr-06, Volume: 49, Issue:7 | Inhibition of human acetyl- and butyrylcholinesterase by novel carbamates of (-)- and (+)-tetrahydrofurobenzofuran and methanobenzodioxepine. |
| AID262755 | Anticholinesterase activity against human plasma BChE | 2006 | Journal of medicinal chemistry, Apr-06, Volume: 49, Issue:7 | Inhibition of human acetyl- and butyrylcholinesterase by novel carbamates of (-)- and (+)-tetrahydrofurobenzofuran and methanobenzodioxepine. |
| AID134728 | Lethal dose was measured at 24 hour in mice following intraperitoneal administration. | 1994 | Journal of medicinal chemistry, Jun-24, Volume: 37, Issue:13 | Syntheses and anticholinesterase activity of tetrahydrobenzazepine carbamates. |
| AID600978 | Inhibition of human erythrocytes AChE | 2011 | European journal of medicinal chemistry, Jun, Volume: 46, Issue:6 | Quinolizidinyl derivatives of bi- and tricyclic systems as potent inhibitors of acetyl- and butyrylcholinesterase with potential in Alzheimer's disease. |
| AID600979 | Inhibition of human plasma AChE | 2011 | European journal of medicinal chemistry, Jun, Volume: 46, Issue:6 | Quinolizidinyl derivatives of bi- and tricyclic systems as potent inhibitors of acetyl- and butyrylcholinesterase with potential in Alzheimer's disease. |
| AID31176 | In vitro inhibitory activity against human AchE (Acetylcholinesterase) | 1992 | Journal of medicinal chemistry, Apr-17, Volume: 35, Issue:8 | Syntheses, resolution, and structure-activity relationships of potent acetylcholinesterase inhibitors: 8-carbaphysostigmine analogues. |
| AID234643 | Selectivity at AChE and BChE | 2002 | Journal of medicinal chemistry, Aug-15, Volume: 45, Issue:17 | Anticholinesterase activity of compounds related to geneserine tautomers. N-Oxides and 1,2-oxazines. |
| AID127610 | Minimal dose to produce side effects was determined for tremor | 1994 | Journal of medicinal chemistry, Jun-24, Volume: 37, Issue:13 | Syntheses and anticholinesterase activity of tetrahydrobenzazepine carbamates. |
| AID31789 | Inhibitory activity against acetylcholinesterase in mice at the dose of 4.8 mg/kg via intraperitoneal administration | 1994 | Journal of medicinal chemistry, Jun-24, Volume: 37, Issue:13 | Syntheses and anticholinesterase activity of tetrahydrobenzazepine carbamates. |
| AID31163 | Ex vivo inhibition of human erythrocyte Acetylcholinesterase. | 2002 | Journal of medicinal chemistry, Aug-15, Volume: 45, Issue:17 | Anticholinesterase activity of compounds related to geneserine tautomers. N-Oxides and 1,2-oxazines. |
| AID44285 | Ex vivo inhibition of human plasma Butyrylcholinesterase. | 2002 | Journal of medicinal chemistry, Aug-15, Volume: 45, Issue:17 | Anticholinesterase activity of compounds related to geneserine tautomers. N-Oxides and 1,2-oxazines. |
| AID262757 | Selectivity for BChE over AChE | 2006 | Journal of medicinal chemistry, Apr-06, Volume: 49, Issue:7 | Inhibition of human acetyl- and butyrylcholinesterase by novel carbamates of (-)- and (+)-tetrahydrofurobenzofuran and methanobenzodioxepine. |
| AID511766 | Inhibition of human AChE by Ellmans test | 2010 | Journal of medicinal chemistry, Sep-09, Volume: 53, Issue:17 | Novel carbamates as orally active acetylcholinesterase inhibitors found to improve scopolamine-induced cognition impairment: pharmacophore-based virtual screening, synthesis, and pharmacology. |
| AID600980 | Inhibition of human erythrocytes BChE | 2011 | European journal of medicinal chemistry, Jun, Volume: 46, Issue:6 | Quinolizidinyl derivatives of bi- and tricyclic systems as potent inhibitors of acetyl- and butyrylcholinesterase with potential in Alzheimer's disease. |
| AID600981 | Inhibition of human plasma BChE | 2011 | European journal of medicinal chemistry, Jun, Volume: 46, Issue:6 | Quinolizidinyl derivatives of bi- and tricyclic systems as potent inhibitors of acetyl- and butyrylcholinesterase with potential in Alzheimer's disease. |
| AID1916839 | Toxicity in mouse assessed as lethal dose | 2022 | European journal of medicinal chemistry, Oct-05, Volume: 240 | Recent advance on carbamate-based cholinesterase inhibitors as potential multifunctional agents against Alzheimer's disease. |
| AID117061 | In vitro lethality measured at 24 hours in mice following intraperitoneal administration | 1992 | Journal of medicinal chemistry, Apr-17, Volume: 35, Issue:8 | Syntheses, resolution, and structure-activity relationships of potent acetylcholinesterase inhibitors: 8-carbaphysostigmine analogues. |
| AID140001 | Percent elevation of ACh level in mouse forebrain following intraperitoneal administration at a dose of 4.8 mg/kg | 1992 | Journal of medicinal chemistry, Apr-17, Volume: 35, Issue:8 | Syntheses, resolution, and structure-activity relationships of potent acetylcholinesterase inhibitors: 8-carbaphysostigmine analogues. |
| AID241560 | Inhibitory concentration against human plasma Butyrylcholinesterase | 2005 | Journal of medicinal chemistry, Feb-24, Volume: 48, Issue:4 | Novel anticholinesterases based on the molecular skeletons of furobenzofuran and methanobenzodioxepine. |
| AID127608 | Minimal dose to produce side effects was determined for salivation | 1994 | Journal of medicinal chemistry, Jun-24, Volume: 37, Issue:13 | Syntheses and anticholinesterase activity of tetrahydrobenzazepine carbamates. |
| AID241692 | Inhibitory concentration against human erythrocyte Acetylcholinesterase | 2005 | Journal of medicinal chemistry, Feb-24, Volume: 48, Issue:4 | Novel anticholinesterases based on the molecular skeletons of furobenzofuran and methanobenzodioxepine. |
| AID1313257 | Binding affinity to AChE in human assessed as enzyme reactivation half life at 8 to 40 mg/kg, po | 2016 | Journal of medicinal chemistry, 07-14, Volume: 59, Issue:13 | Fatty Acid Amide Hydrolase (FAAH), Acetylcholinesterase (AChE), and Butyrylcholinesterase (BuChE): Networked Targets for the Development of Carbamates as Potential Anti-Alzheimer's Disease Agents. |
| AID31174 | In vitro inhibitory activity against human acetylcholinesterase | 1994 | Journal of medicinal chemistry, Jun-24, Volume: 37, Issue:13 | Syntheses and anticholinesterase activity of tetrahydrobenzazepine carbamates. |
| AID1916837 | Binding affinity to AChE (unknown origin) assessed as inhibition constant | 2022 | European journal of medicinal chemistry, Oct-05, Volume: 240 | Recent advance on carbamate-based cholinesterase inhibitors as potential multifunctional agents against Alzheimer's disease. |
| AID1796572 | Cholinesterase Inhibition Assay from Article 10.1021/jm010491d: \\Anticholinesterase activity of compounds related to geneserine tautomers. N-Oxides and 1,2-oxazines.\\ | 2002 | Journal of medicinal chemistry, Aug-15, Volume: 45, Issue:17 | Anticholinesterase activity of compounds related to geneserine tautomers. N-Oxides and 1,2-oxazines. |
| [information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||||
| Timeframe | Studies, This Drug (%) | All Drugs % |
|---|---|---|
| pre-1990 | 3 (4.23) | 18.7374 |
| 1990's | 52 (73.24) | 18.2507 |
| 2000's | 11 (15.49) | 29.6817 |
| 2010's | 3 (4.23) | 24.3611 |
| 2020's | 2 (2.82) | 2.80 |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||
According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be weak demand-to-supply ratio for research on this compound.
| This Compound (11.38) All Compounds (24.57) |
| Publication Type | This drug (%) | All Drugs (%) |
|---|---|---|
| Trials | 12 (15.38%) | 5.53% |
| Reviews | 3 (3.85%) | 6.00% |
| Case Studies | 0 (0.00%) | 4.05% |
| Observational | 0 (0.00%) | 0.25% |
| Other | 63 (80.77%) | 84.16% |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||