Intravenous 2-Chloroprocaine in Treatment of Chronic Pain

Schnapp, Moacir; Mays, Kit S.; North, William C.

doi:10.1213/00000539-198111000-00018

Cited by 19 publications

(6 citation statements)

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“…Procaine, lidocaine and bupivacaine, administered slowly by i.v., as well as orally-administered tocainide, suppress certain types of pain in humans. These include neoplastic [ 55 ], post-operative [ 56 - 62 ], post-traumatic [ 63 ], neuralgic [ 64 , 65 ], muscular [ 66 , 67 ], adiposa dolorosa [ 68 - 71 ], labour [ 72 ], and pain due to administration of radiological contrast agents [ 73 ]. Local anesthetics, by blocking presynaptic muscarinic autoreceptors, increase endogenous ACh release.…”

Section: Analgesia Induced By Enhancers Of Ach Releasementioning

confidence: 99%

Analgesic and Antineuropathic Drugs Acting Through Central Cholinergic Mechanisms

Bartolini¹,

Mannelli²,

Ghelardini

2011

RPCN

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The role of muscarinic and nicotinic cholinergic receptors in analgesia and neuropathic pain relief is relatively unknown. This review describes how such drugs induce analgesia or alleviate neuropathic pain by acting on the central cholinergic system. Several pharmacological strategies are discussed which increase synthesis and release of acetylcholine (ACh) from cholinergic neurons. The effects of their acute and chronic administration are described. The pharmacological strategies which facilitate the physiological functions of the cholinergic system without altering the normal modulation of cholinergic signals are highlighted. It is proposed that full agonists of muscarinic or nicotinic receptors should be avoided. Their activation is too intense and un-physiological because neuronal signals are distorted when these receptors are constantly activated. Good results can be achieved by using agents that are able to a) increase ACh synthesis, b) partially inhibit cholinesterase activity c) selectively block the autoreceptor or heteroreceptor feedback mechanisms. Activation of M1 subtype muscarinic receptors induces analgesia. Chronic stimulation of nicotinic (N1) receptors has neuronal protective effects. Recent experimental results indicate a relationship between repeated cholinergic stimulation and neurotrophic activation of the glial derived neurotrophic factor (GDNF) family. At least 9 patents covering novel chemicals for cholinergic system modulation and pain control are discussed.

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Section: Analgesia Induced By Enhancers Of Ach Releasementioning

confidence: 99%

Analgesic and Antineuropathic Drugs Acting Through Central Cholinergic Mechanisms

Bartolini¹,

Mannelli²,

Ghelardini

2011

RPCN

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“…These include neoplastic pain (Cavallini & Beltrami, 1968), post-operative pain (McLachlin, 1945; Keats et al, 1951;De Clive-Lowe, 1958;Bartlett & Hutaserani, 1961;Nalda Felipe et al, 1977;De Gaudio et al, 1978;Marchisio, 1980), post-traumatic pain (Schnapp, 1981), neuralgic pain (Boas et al, 1982;Lindblom & Lindstrdm, 1984), muscular pain (Usubiaga et al, 1967;Haldia et al, 1973), adiposa dolorosa (Iwane et al, 1976;Lindstr6m & Lindblom, 1987;Kastrup et al, 'Author for correspondence.…”

Section: Introductionmentioning

confidence: 99%

“…It has been reported that various local anaesthetics (procaine, lignocaine, bupivacaine), administered by a slow intravenous route, as well as orally-administered tocainide, suppress certain types of pain in humans. These include neoplastic pain (Cavallini & Beltrami, 1968), post-operative pain (McLachlin, 1945;Keats et al, 1951;De Clive-Lowe, 1958;Bartlett & Hutaserani, 1961;Nalda Felipe et al, 1977;De Gaudio et al, 1978;Marchisio, 1980), post-traumatic pain (Schnapp, 1981), neuralgic pain (Boas et al, 1982;Lindblom & Lindstrdm, 1984), muscular pain (Usubiaga et al, 1967;Haldia et al, 1973), adiposa dolorosa (Iwane et al, 1976;Lindstr6m & Lindblom, 1987;Kastrup et al, 'Author for correspondence. 1987; , labour pains (Gilbert et al, 1951) and pain due to administration of radiological contrast media (Gerlock et al, 1979).…”

Section: Introductionmentioning

confidence: 99%

Antinociception induced by systemic administration of local anaesthetics depends on a central cholinergic mechanism

Bartolini

Galli

Ghelardini

et al. 1987

British J Pharmacology

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The antinociceptive effects of systemically‐administered procaine, lignocaine and bupivacaine were examined in mice and rats by using the hot‐plate, writhing and tail flick tests. In both species all three local anaesthetics produced significant antinociception which was prevented by atropine (5 mg kg−1, i.p.) and by hemicholinium‐3 (1 μg per mouse, i.c.v.), but not by naloxone (3 mg kg−1, i.p.), α‐methyl‐p‐tyrosine (100 mg kg−1, s.c.), reserpine (2 mg kg−1, i.p.) or atropine methylbromide (5.5 mg kg−1, i.p.). Atropine (5 mg kg−1, i.p.) which totally antagonized oxotremorine (40 μg kg−1, s.c.) antinociception did not modify morphine (5 mg kg−1, s.c.) or baclofen (4 mg kg−1, s.c.) antinociception. On the other hand, hemicholinium, which antagonized local anaesthetic antinociception, did not prevent oxotremorine, morphine or baclofen antinociception. Intracerebroventricular injection in mice of procaine (200 μg), lignocaine (150 μg) and bupivacaine (25 μg), doses which were largely ineffective by parenteral routes, induced an antinociception whose intensity equalled that obtainable subcutaneously. Moreover, the i.c.v. injection of antinociceptive doses did not impair performance on the rota‐rod test. Concentrations below 10−10 m of procaine, lignocaine and bupivacaine did not evoke any response on the isolated longitudinal muscle strip of guinea‐pig ileum, or modify acetylcholine (ACh)‐induced contractions. On the other hand, they always increased electrically‐evoked twitches. The same concentrations of local anaesthetics which induced antinociception did not inhibit acetylcholinesterase (AChE) in vitro. On the basis of the above findings and the existing literature, a facilitation of cholinergic transmission by the local anaesthetics is postulated; this could be due to blockade of presynaptic muscarinic receptors.

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“…19 Procaine and 2-chloroprocaine, two ester local anesthetics administered intravenously, intramuscularly, or subcutaneously, will be hydrolyzed by plasma butyrylcholinesterase (pseudocholinesterase), but sufficient ester will penetrate the BBB to induce significant CNS effects and in some cases temporary relief of pain. 20 Therefore, even with plasma esterase concentrations 20–100 fold greater than CSF levels, it is still possible to safely introduce an ester compound into the central nervous system. 21…”

Section: After Degradation By Plasma Esterases Would Enough Gaba Estmentioning

confidence: 99%

Selected Gamma Aminobutyric Acid (GABA) Esters may Provide Analgesia for Some Central Pain Conditions

Goldberg

2010

Perspect Medicin Chem

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Central pain is an enigmatic, intractable condition, related to destruction of thalamic areas, resulting in likely loss of inhibitory synaptic transmission mediated by GABA. It is proposed that treatment of central pain, a localized process, may be treated by GABA supplementation, like Parkinson’s disease and depression. At physiologic pH, GABA exists as a zwitterion that is poorly permeable to the blood brain barrier (BBB). Because the pH of the cerebral spinal fluid (CSF) is acidic relative to the plasma, ion trapping may allow a GABA ester prodrug to accumulate and be hydrolyzed within the CSF. Previous investigations with ester local anesthetics may be applicable to some GABA esters since they are weak bases, hydrolyzed by esterases and cross the BBB. Potential non-toxic GABA esters are discussed. Many GABA esters were investigated in the 1980s and it is hoped that this paper may spark renewed interest in their development.

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Intravenous 2-Chloroprocaine in Treatment of Chronic Pain

Cited by 19 publications

References 0 publications

Analgesic and Antineuropathic Drugs Acting Through Central Cholinergic Mechanisms

Analgesic and Antineuropathic Drugs Acting Through Central Cholinergic Mechanisms

Antinociception induced by systemic administration of local anaesthetics depends on a central cholinergic mechanism

Selected Gamma Aminobutyric Acid (GABA) Esters may Provide Analgesia for Some Central Pain Conditions

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