Phase I Safety Assessment of Intrathecal Neostigmine Methylsulfate in Humans

Hood, David D.; Eisenach, James C.; Tuttle, Robin

doi:10.1097/00000542-199502000-00003

Cited by 274 publications

(216 citation statements)

References 24 publications

Supporting

Mentioning

191

Contrasting

Unclassified

Order By: Relevance

“…Mean oxygen saturation (SpO 2 ) and respiratory rate were comparable between the three groups and other similar studies 8,10 with no patient developing hypoxemia (SpO 2 < 90%).There is no reported evidence of respiratory depression with the use of intrathecal neostigmine.…”

Section: Discussionsupporting

confidence: 56%

“…None of the patients developed symptomatic bradycardia (<50 bpm) or hypotension defined as a decrease in mean arterial blood pressure by ≥ 20%. Lauretti et al 9 showed similar observations but our study was in contrast to Hood et al 8 who showed that spinally administered cholinergic agonist or cholinesterase inhibitors increase blood pressure and heart rate. The small dose (50-150 µg of neostigmine) could explain the lack of cardiovascular stimulation seen in our study.…”

Section: Discussionsupporting

confidence: 54%

“…Intrathecal neostigmine, the cholinergic agent (a cholinesterase inhibitor) causes analgesia in humans. 8 Acetylcholine being released from preganglionic sympathetic ganglia has been shown to have action at other spinal sites like inhibition of motor neuron activity and excitation of sympathetic outflow. 2 Spinal neostigmine is advantageous over other currently used spinal drugs as it causes no hypotension (excitation of sympathetic outflow), no sedation, no respiratory depression or neurological dysfunction.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Evaluation of intrathecal neostigmine in different doses added to bupivacaine for postoperative analgesia

Bhat¹,

Ommid

Gupta

et al. 2011

Sri Lankan J Anaesthesiol

View full text Add to dashboard Cite

show abstract

Section: Discussionsupporting

confidence: 56%

Section: Discussionsupporting

confidence: 54%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Evaluation of intrathecal neostigmine in different doses added to bupivacaine for postoperative analgesia

Bhat¹,

Ommid

Gupta

et al. 2011

Sri Lankan J Anaesthesiol

View full text Add to dashboard Cite

show abstract

“…It has long been known that the direct and indirect activation of the cholinergic system produces analgesia in both animals (1,2,9,(16)(17)(18)21,23,24) and humans (20). Because sumatriptan is endowed with cholinergic antinociceptive properties and 8-OH-DPAT enhances ACh release, the goals of the present study were to explore whether other 5-HT 1A agonists, such as gepirone and 8-OH-DPAT, were able to increase the pain threshold in mice and then investigate whether a cholinergic mechanism underlies 5-HT 1A antinociception.…”

mentioning

confidence: 99%

5-HT1A Agonists Induce Central Cholinergic Antinociception

Galeotti

Ghelardini

Bartolini

1997

Pharmacology Biochemistry and Behavior

View full text Add to dashboard Cite

GALEOTTI, N., C. GHELARDINI AND A. BARTOLINI. 5-HT 1A agonists induce central cholinergic antinociception. PHARMACOL BIOCHEM BEHAV 57 (4) 835-841, 1997.-The antinociceptive effects of the 5-HT 1A agonists buspirone [3 mg/kg intraperitoneally (IP)], gepirone (3-6 mg/kg IP), and 8-OH-DPAT [3-5 mg/kg IP; 1-3 g per mouse intracerebroventricularly (ICV)] were examined in mice by using the hot-plate (thermal stimulus) and abdominal constriction (chemical stimulus) tests. Buspirone, gepirone, and 8-OH-DPAT produced significant antinociception, which was prevented by atropine (5 mg/kg IP), the ACh depletor hemicholinium-3 (1 g per mouse ICV), and the 5-HT 1A antagonist NAN 190 (0.5 g per mouse ICV), but not by naloxone (1 mg/kg IP), the GABA B antagonist CGP 35348 (100 mg/kg IP), and pertussis toxin (0.25 g per mouse ICV). NAN 190, which totally antagonized buspirone, gepirone, and 8-OH-DPAT antinociception, did not modify the analgesic effect of morphine (5 mg/kg subcutaneously). In the antinociceptive dose range, none of the 5HT 1A agonists impaired mouse performance evaluated by rota-rod and hole board tests. On the basis of these data, it can be postulated that buspirone, gepirone, and 8-OH-DPAT exert an antinociceptive effect mediated by a central amplification of cholinergic transmission. © 1997 Elsevier Science Inc. 8-OH-DPATBuspirone Gepirone 5-HT 1A receptors ACh Cholinergic neurotransmission Antinociception Analgesia THE nonbenzodiazepine anxiolytic drugs buspirone, gepirone, and 8-OH-DPAT are agonists of the serotoninergic 5-HT 1A receptors in the central nervous system. Serotonin 5-HT 1A sites are localized predominantly on the axon terminals of serotoninergic neurons. They function as autoreceptors (14), and their stimulation leads to the disinhibition of the cholinergic system that is tonically inhibited by tryptaminergic control (11). Bianchi et al. (4) demonstrated that the full 5-HT 1A agonist 8-OH-DPAT was able to increase ACh release from the cerebral cortex of freely moving guinea pigs. Recent studies have shown that buspirone, given systemically, produces antinociception in several pain tests in rats (12). Giordano and Rogers (13) reported that buspirone-induced analgesia may be a nonopioid, adrenally mediated co-and/or epi-phenomenon to core hypothermia evoked by 5-HT 1A receptor agonism. Recently, it was reported that sumatriptan, another 5-HT 1A agonist, was able to induce antinociception in mice and rats through a cholinergic mechanism (3).It has long been known that the direct and indirect activation of the cholinergic system produces analgesia in both animals (1,2,9,16-18,21,23,24) and humans (20). Because sumatriptan is endowed with cholinergic antinociceptive properties and 8-OH-DPAT enhances ACh release, the goals of the present study were to explore whether other 5-HT 1A agonists, such as gepirone and 8-OH-DPAT, were able to increase the pain threshold in mice and then investigate whether a cholinergic mechanism underlies 5-HT 1A antinociception. Moreover, we examined whether such antinoci...

show abstract

“…The acetyl-choline esterase inhibitor neostigmine, has demonstrated a dose-dependant analgesia following spinal or epidural administration [11,12]. However, this central delivery of neostigmine is limited by dose-related side effects such as nausea, vomiting, pruritis, caused by cephalad spread of neostigmine in the cerebrospinal fluid [13,14].…”

Section: Introductionmentioning

confidence: 99%

Pain relief following Arthroscopy - a comparative study of Intra-articular Bupivacaine, Morphine and Neostigmine

Datta

Madhusudanan²

2004

Medical Journal Armed Forces India

View full text Add to dashboard Cite

Pain after arthroscopy is quite distressing. Intra-articular bupivacaine produces transient analgesia and reports of analgesia using intra-articular opioids have produced conflicting results. Recently, spinal administration of neostigmine was shown to produce dose-dependant analgesia. However, this was limited by adverse effects. The purpose of this study was to compare the effects on intra-articular neostigmine, bupivacaine and morphine. 75 patients were randomized to receive intra-articular saline, bupivacaine, morphine, neostigmine and bupivacaine-neostigmine after arthroscopic surgery under spinal anaesthesia. Visual analog pain scores (VAS), duration of analgesia as defined as time for first demand for parenteral opioids and the total subsequent consumption of morphine was evaluated. Intra-articular bupivacaine resulted in significant VAS reduction at one and four hours as compared to those receiving intra-articular saline and morphine. Analgesia lasted longer after 500ugm intra-articular neostigmine as compared with bupivacaine, morphine or saline. The need for supplementary analgesia was lowest in the neostigmine group as compared to the other groups. No significant difference was found if bupivacaine was added to neostigmine. Among all the groups, no significant side-effects were observed. MJAFI 2004; 60 : 123-127

show abstract

Phase I Safety Assessment of Intrathecal Neostigmine Methylsulfate in Humans

Cited by 274 publications

References 24 publications

Evaluation of intrathecal neostigmine in different doses added to bupivacaine for postoperative analgesia

Evaluation of intrathecal neostigmine in different doses added to bupivacaine for postoperative analgesia

5-HT1A Agonists Induce Central Cholinergic Antinociception

Pain relief following Arthroscopy - a comparative study of Intra-articular Bupivacaine, Morphine and Neostigmine

Contact Info

Product

Resources

About