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Chemical Compound Review

pyridostigmine     (1-methylpyridin-5-yl) N,N-dimethylcarbamate

Synonyms: Regonol, Mestinon-SR, Lopac-P-9797, CHEMBL1115, SureCN1317, ...
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Disease relevance of pyridostigmine


Psychiatry related information on pyridostigmine


High impact information on pyridostigmine

  • Here we report that after mice were subjected to a forced swim protocol (shown previously to simulate stress), an increase in blood-brain barrier permeability reduced the pyridostigmine dose required to inhibit mouse brain AChE activity by 50% to less than 1/100th of the usual dose [11].
  • Unexpectedly, under a similar regimen, pyridostigmine administration during the Persian Gulf War resulted in a greater than threefold increase in the frequency of reported central nervous system symptoms [11].
  • Under these conditions, peripherally administered pyridostigmine increased the brain levels of c-fos oncogene and AChE mRNAs [11].
  • CONCLUSION: Three new findings are reported: 1) FM patients have a reduced GH response to exercise, 2) pyridostigmine reverses this impaired response, and 3) defective GH secretion in FM can occur in patients with normal IGF-1 levels [12].
  • Effect of pyridostigmine bromide on serum bromide concentration and the anion gap [13].

Chemical compound and disease context of pyridostigmine


Biological context of pyridostigmine


Anatomical context of pyridostigmine


Associations of pyridostigmine with other chemical compounds

  • Therefore, only GHRH combined with PD or ARG may be able to clearly differentiate normal children from patients with GH deficiency, though a normal GH response to these tests cannot rule out the existence of GH hyposecretory state because of hypothalamic dysfunction [28].
  • In other experiments, the administration of propranolol (PRO; 40 mg, orally), or clonidine (CLO; 0.300 mg, orally), or pyridostigmine (PD; 120 mg, orally) was followed by GHRH administration 60 min later [29].
  • PD increased (P < 0.05) GH (change in area under curves, mean +/- SEM, 790.9 +/- 229.3 microg(*)min/liter) but did not modify insulin and glucose levels [30].
  • After nocturnal DEX administration, both PRO and CLO, but not PD, were able to reverse the inhibitory effect of DEX on GHRH-elicited GH release (peaks: 39 +/- 5.5, 25.9 +/- 3.9 and 12.9 +/- 3.1, micrograms/L; DEX + PRO, DEX + CLO, and DEX + PD, respectively) [29].
  • Multiple regression analysis also revealed a significant positive correlation between progesterone levels and GH response to pyridostigmine (P less than 0.02) [31].

Gene context of pyridostigmine

  • In contrast, pretreatment with yohimbine significantly (P less than 0.05) blunted the pyridostigmine-induced enhancement of GHRH-elicited GH release [32].
  • Conversely, preincubation of CYP3A4 with pyridostigmine bromide increased metabolite levels of 6beta-OHTST and 2beta-OHTST [33].
  • To block lipolysis and hypothalamic somatostatin release, subjects in group B received acipimox, an antilipolytic agent (500 mg), and pyridostigmine, an acetylcholinesterase inhibitor (60 mg), during the 6 h before iv GHRH [34].
  • The PD-induced ghrelin peak did not precede that of GH [30].
  • The FA1 responses to placebo were not significantly different from the responses to the combination of pyridostigmine and GHRH [35].

Analytical, diagnostic and therapeutic context of pyridostigmine


  1. Bromide intoxication secondary to pyridostigmine bromide therapy. Rothenberg, D.M., Berns, A.S., Barkin, R., Glantz, R.H. JAMA (1990) [Pubmed]
  2. Pyridostigmine bromide and constipation in Parkinson's disease. Sadjadpour, K. JAMA (1983) [Pubmed]
  3. Endogenous growth hormone (GH)-releasing hormone is required for GH responses to pharmacological stimuli. Jaffe, C.A., DeMott-Friberg, R., Barkan, A.L. J. Clin. Invest. (1996) [Pubmed]
  4. A transcription-activating polymorphism in the ACHE promoter associated with acute sensitivity to anti-acetylcholinesterases. Shapira, M., Tur-Kaspa, I., Bosgraaf, L., Livni, N., Grant, A.D., Grisaru, D., Korner, M., Ebstein, R.P., Soreq, H. Hum. Mol. Genet. (2000) [Pubmed]
  5. Pyridostigmine for fibromyalgia: comment on the article by Paiva and a historical vignette. Wallace, D.J. Arthritis Rheum. (2003) [Pubmed]
  6. Genetic predisposition to adverse consequences of anti-cholinesterases in 'atypical' BCHE carriers. Loewenstein-Lichtenstein, Y., Schwarz, M., Glick, D., Nørgaard-Pedersen, B., Zakut, H., Soreq, H. Nat. Med. (1995) [Pubmed]
  7. Elevated growth hormone responses to pyridostigmine in obsessive-compulsive disorder: evidence of cholinergic supersensitivity. Lucey, J.V., Butcher, G., Clare, A.W., Dinan, T.G. The American journal of psychiatry. (1993) [Pubmed]
  8. Arginine but not pyridostigmine, a cholinesterase inhibitor, enhances the GHRH-induced GH rise in patients with anorexia nervosa. Ghigo, E., Arvat, E., Gianotti, L., Nicolosi, M., Valetto, M.R., Avagnina, S., Bellitti, D., Rolla, M., Müller, E.E., Camanni, F. Biol. Psychiatry (1994) [Pubmed]
  9. Growth hormone responses to pyridostigmine in schizophrenia: evidence for cholinergic dysfunction. O'Keane, V., Abel, K., Murray, R.M. Biol. Psychiatry (1994) [Pubmed]
  10. Enhanced growth hormone responses to pyridostigmine challenge in patients with panic disorder. Cooney, J.M., Lucey, J.V., Dinan, T.G. The British journal of psychiatry : the journal of mental science. (1997) [Pubmed]
  11. Pyridostigmine brain penetration under stress enhances neuronal excitability and induces early immediate transcriptional response. Friedman, A., Kaufer, D., Shemer, J., Hendler, I., Soreq, H., Tur-Kaspa, I. Nat. Med. (1996) [Pubmed]
  12. Impaired growth hormone secretion in fibromyalgia patients: evidence for augmented hypothalamic somatostatin tone. Paiva, E.S., Deodhar, A., Jones, K.D., Bennett, R. Arthritis Rheum. (2002) [Pubmed]
  13. Effect of pyridostigmine bromide on serum bromide concentration and the anion gap. Faradji-Hazan, V., Oster, J.R., Fedeman, D.G., Clerch, A.R., Perez, G.O. J. Am. Soc. Nephrol. (1991) [Pubmed]
  14. Effect of growth hormone (GH)-releasing hormone (GHRH), atropine, pyridostigmine, or hypoglycemia on GHRP-6-induced GH secretion in man. Peñalva, A., Carballo, A., Pombo, M., Casanueva, F.F., Dieguez, C. J. Clin. Endocrinol. Metab. (1993) [Pubmed]
  15. Treatment of Lambert-Eaton syndrome: 3,4-diaminopyridine and pyridostigmine. Lundh, H., Nilsson, O., Rosén, I. Neurology (1984) [Pubmed]
  16. Clinical pharmacokinetics of cholinesterase inhibitors. Aquilonius, S.M., Hartvig, P. Clinical pharmacokinetics. (1986) [Pubmed]
  17. Hemicholinium-3 congeners as potential antagonists to organophosphate-induced toxicity. Cannon, J.G., Sahin, M.F., Long, J.P., Flynn, J.R., Bhatnagar, R.K. J. Med. Chem. (1990) [Pubmed]
  18. Prolonged effect of succinylcholine after neostigmine and pyridostigmine administration in patients with renal failure. Bishop, M.J., Hornbein, T.F. Anesthesiology (1983) [Pubmed]
  19. Pyridostigmine kinetics in healthy subjects and patients with myasthenia gravis. Breyer-Pfaff, U., Maier, U., Brinkmann, A.M., Schumm, F. Clin. Pharmacol. Ther. (1985) [Pubmed]
  20. Plasma pyridostigmine levels in patients with myasthenia gravis. Calvey, T.N., Chan, K. Clin. Pharmacol. Ther. (1977) [Pubmed]
  21. The pharmacokinetics of pyridostigmine. Cohan, S.L., Pohlmann, J.L., Mikszewski, J., O'Doherty, D.S. Neurology (1976) [Pubmed]
  22. Pyridostigmine kinetics with and without renal function. Cronnelly, R., Stanski, D.R., Miller, R.D., Sheiner, L.B. Clin. Pharmacol. Ther. (1980) [Pubmed]
  23. Evidence that enhancement of cholinergic tone increases basal plasma levels of calcitonin gene-related peptide in normal man. Trasforini, G., Margutti, A., Vergnani, L., Ambrosio, M.R., Valentini, A., Rossi, R., Portaluppi, F., Degli Uberti, E.C. J. Clin. Endocrinol. Metab. (1994) [Pubmed]
  24. The nature of the interactions of pyridostigmine with the nicotinic acetylcholine receptor-ionic channel complex. I. Agonist, desensitizing, and binding properties. Pascuzzo, G.J., Akaike, A., Maleque, M.A., Shaw, K.P., Aronstam, R.S., Rickett, D.L., Albuquerque, E.X. Mol. Pharmacol. (1984) [Pubmed]
  25. A multicenter, randomized, double-blinded trial of pyridostigmine in postpolio syndrome. Trojan, D.A., Collet, J.P., Shapiro, S., Jubelt, B., Miller, R.G., Agre, J.C., Munsat, T.L., Hollander, D., Tandan, R., Granger, C., Robinson, A., Finch, L., Ducruet, T., Cashman, N.R. Neurology (1999) [Pubmed]
  26. Effect of central cholinergic neurotransmission enhancement by pyridostigmine on the growth hormone secretion elicited by clonidine, arginine, or hypoglycemia in normal and obese subjects. Cordido, F., Dieguez, C., Casanueva, F.F. J. Clin. Endocrinol. Metab. (1990) [Pubmed]
  27. Newborn infants to myasthenic mothers: a clinical study and an investigation of acetylcholine receptor antibodies in 17 children. Lefvert, A.K., Osterman, P.O. Neurology (1983) [Pubmed]
  28. Reliability of provocative tests to assess growth hormone secretory status. Study in 472 normally growing children. Ghigo, E., Bellone, J., Aimaretti, G., Bellone, S., Loche, S., Cappa, M., Bartolotta, E., Dammacco, F., Camanni, F. J. Clin. Endocrinol. Metab. (1996) [Pubmed]
  29. Glucocorticoids may inhibit growth hormone release by enhancing beta-adrenergic responsiveness in hypothalamic somatostatin neurons. Lima, L., Arce, V., Diaz, M.J., Tresguerres, J.A., Devesa, J. J. Clin. Endocrinol. Metab. (1993) [Pubmed]
  30. Acetylcholine regulates ghrelin secretion in humans. Broglio, F., Gottero, C., Van Koetsveld, P., Prodam, F., Destefanis, S., Benso, A., Gauna, C., Hofland, L., Arvat, E., van der Lely, A.J., Ghigo, E. J. Clin. Endocrinol. Metab. (2004) [Pubmed]
  31. Sex steroid priming effects on growth hormone response to pyridostigmine throughout the menstrual cycle. O'Keane, V., Dinan, T.G. J. Clin. Endocrinol. Metab. (1992) [Pubmed]
  32. Evidence that alpha 2-adrenergic pathways play a major role in growth hormone (GH) neuroregulation: alpha 2-adrenergic agonism counteracts the inhibitory effect of muscarinic cholinergic receptor blockade on the GH response to GH-releasing hormone, while alpha 2-adrenergic blockade diminishes the potentiating effect of increased cholinergic tone on such stimulation in normal men. Devesa, J., Diaz, M.J., Tresguerres, J.A., Arce, V., Lima, L. J. Clin. Endocrinol. Metab. (1991) [Pubmed]
  33. Inhibition and activation of the human liver microsomal and human cytochrome P450 3A4 metabolism of testosterone by deployment-related chemicals. Usmani, K.A., Rose, R.L., Hodgson, E. Drug Metab. Dispos. (2003) [Pubmed]
  34. Growth hormone (GH) autofeedback on GH response to GH-releasing hormone. Role of free fatty acids and somatostatin. Pontiroli, A.E., Lanzi, R., Monti, L.D., Sandoli, E., Pozza, G. J. Clin. Endocrinol. Metab. (1991) [Pubmed]
  35. Fetal antigen 1 in healthy adults and patients with pituitary disease: relation to physiological, pathological, and pharmacological GH levels. Andersen, M., Jensen, C.H., Støving, R.K., Larsen, J.B., Schrøder, H.D., Teisner, B., Hagen, C. J. Clin. Endocrinol. Metab. (2001) [Pubmed]
  36. Pyridostigmine used as a nerve agent pretreatment under wartime conditions. Keeler, J.R., Hurst, C.G., Dunn, M.A. JAMA (1991) [Pubmed]
  37. Descending paralysis resulting from occult wound botulism. Rapoport, S., Watkins, P.B. Ann. Neurol. (1984) [Pubmed]
  38. Malabsorption of pyridostigmine in patients with myasthenia gravis. Cohan, S.L., Dretchen, K.L., Neal, A. Neurology (1977) [Pubmed]
  39. Eye movement fatigue in myasthenia gravis. Spooner, J.W., Baloh, R.W. Neurology (1979) [Pubmed]
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