3-substituted GABA analogs with central nervous system activity: A review

Medicinal Research Reviews

Volumn 19, Issue 2, 1999, Pages 149-177

  Bryans, Justin S ^a   Wustrow, David J ^b  

^a Parke Davis Neurosci Res Center   (United Kingdom)

^b PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANXIOLYTIC AGENT; CARRAGEENAN; GABAPENTIN; MORPHINE DERIVATIVE; N METHYL DEXTRO ASPARTIC ACID; PIPERAZINE DERIVATIVE; PREGABALIN; SUBSTANCE P;

AMYOTROPHIC LATERAL SCLEROSIS; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTICONVULSANT ACTIVITY; ATAXIA; CONVULSION; DIABETIC NEPHROPATHY; DIPLOPIA; DRUG EFFICACY; DRUG INDICATION; DRUG POTENCY; DRUG TOLERANCE; EPILEPSY; FATIGUE; HUMAN; MOUSE; MULTIPLE SCLEROSIS; NONHUMAN; NYSTAGMUS; PARKINSONISM; POSTOPERATIVE PAIN; RAT; RESTLESS LEGS SYNDROME; REVIEW; SOMNOLENCE; SPASTICITY; SYMPATHETIC DYSTROPHY; TREMOR; VERTIGO;

ACETIC ACIDS; AMINES; ANALGESICS; ANIMALS; ANTICONVULSANTS; CYCLOHEXANECARBOXYLIC ACIDS; GAMMA-AMINOBUTYRIC ACID; HUMANS; HYPERALGESIA; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0033018825     PISSN: 01986325     EISSN: None     Source Type: Journal    
DOI: 10.1002/(SICI)1098-1128(199903)19:2<149::AID-MED3>3.0.CO;2-B     Document Type: Review

References (118)

1. Satzinger G. Antiepileptics from gamma-aminobutyric acid. Arzneim-Forsch 1994; 44:261-266.
2. Kerr D, Ong J. GABAB receptors. Pharmacol-Ther 1995;67:187-246.
3. Campbell SK, Almeida GL, Penn RD, Corcos DM. The effects of intrathecally administered baclofen on function in patients with spasticily. Phys-Ther 1995;75:352-362.
4. Sabers A, Lennart G. Pharmacology of vigabatrin. Pharmacol Toxicol (Copenhagen) 1992;70:237-243.
5. Ben-Menachem E. Vigabatrin. Epilepsia (NY) 1995;36:S95-S104.
6. Worms P, Depoortere H, Durand A, Morselli PL, Lloyd KG, Bartholini G. γ-Aminobutyric acid (GABA) receptor stimulation. I. Neuropharmacological profiles of progabide (SL 76002) and SL 75102, with emphasis on their anticonvulsant spectra. J Pharmacol Exp Ther 1982;220:660-671.
7. Bartoszyk GD, Meyerson N, Reimann W, Satzinger G, Von Hodenberg A. Gabapentin [pharmacology]. Curr Probl Epilepsy 1986;4:147-163.
8. Hartenstein J, Satzinger G, Herrmann M. Cyclic amino acid derivatives. German patent 2626467. 1977.
9. Satzinger G, Hartenstein J, Herrmann M, Heldt W. Cyclic amino acids. German patent 2543821. 1977.
10. Gabapentin. Drugs of the Future 1984;9:418-419.
11. Griffiths G, Mettler H, Mills LS, Previdoli F. Novel syntheses of gabapentin via addition of hydrocyanic acid to cyclohexylidenemalonate or cyano(cyclohexylidene)acetate. Helv Chim Acta 1991;74:309-314.
12. Jennings RA, Johnson DR, Seamans RE, Zeller JR. Preparation of 1-(aminomethyl)cycloalkaneacetic acids. US patent 5319135. 1994.
13. Radulovic LL, Taylor CP, Walker RM. The preclinical pharmacology, pharmacokinetics and toxicology of gabapentin. Drugs Today 1995;31:597-611.
14. Goa KL, Sorkin EM, Gabapentin: a review of its pharmacological properties and clinical potential in epilepsy. Drugs 1993;46:409-427.
15. Mellick GA, Mellick LB. Reflex sympathetic dystrophy treated with gabapentin. Arch Phys Med Rehabil 1997;78:98-105.
16. Rosner H, Rubin L, Kestenbaum A. Gabapentin adjunctive therapy in neuropathic pain states. Clin J Pain 1996;12:56-58
17. Bennett GJ. A peripheral mononcuropathy in rat that produces disorders of pain sensation like those seen in man. Pain 1988;33:87-107.
18. Xiao WH, Bennett GJ. Gabapentin has an antinociceptive effect mediated via a spinal site of action in a rat model of painful peripheral neuropathy. Analgesia 1996;2(5/6):267-273.
19. Hunter JC, Gogas KR, Hedley LR, Jacobson LO, Kassotakis L, Thompson J, Fontana DJ. The effect of novel anti-epileptic drugs in rat experimental models of acute and chronic pain. Eur J Pharmacol 1997; 324:153-160.
20. Kim SH, Chung JM. An experimental neuropathy produced by segmental spinal nerve ligation. Pain 1992; 50:355-363.
21. Hwang JH, Yaksh TL. Effect of subarachnoid gabapentin on tactile-evoked allodynia in a surgically induced neuropathic pain model in the rat. Reg Anesth 1997;22:249-256.
22. Chapman V, Suzuki R, Chamarette HLC, Rygh LJ, Dickenson AH. Effects of systemic carbamazepine and gabapentin on spinal neuronal responses in spinal nerve ligated rats. Pain 1998;75:261-272.
23. Singh L, Field MJ, Ferris P, Hunter JC, Oles RJ, Williams RG, Woodruff GN. The antiepileptic agent gabapentin (Neurontin) possesses anxiolytic-like and antinociceptive actions that are reversed by D-serine. Psychopharmacology 1996;127:1-9.
24. Field MJ, Oles RJ, Lewis AS, McCleary S, Hughes J, Singh L. Gabapentin (neurontin) and S-(+)-3-isobutylgaba represent a novel class of selective antihyperalgesic agents. Br J Pharmacol 1997;121:1513-1522.
25. Shimoyumu N, Shimoyama M, Davis AM, Inturrisi CE, Elliott KJ. Spinal gabapentin is antinociceptive in the rat formalin test. Neurosci Lett 1997;222:65-67.
26. Carlton SM, Zhou S. Attenuation of formalin-induced nociceptive behaviors following local peripheral injection of gabapentin. Pain 1998;76:201-207.
27. Stanfa LC, Singh L, Williams RG, Dickenson AH. Gabapentin, ineffective in normal rats, markedly reduces C-fiber evoked responses after inflammation. NeuroReport 1997;8:587-590.
28. Gould III, HJ, Gould TN, Reeb SC, Paul D. The effect of gabapentin on inflammatory pain in rats. Analgesia 1997;3(3):131-139.
29. Slart RS, Sorkin L, Yaksh T, Yu AL. An animal model of pain produced by systemic administration of an immunotherapeutic anti-ganglioside antibody. Pain 1997;69:119-125.
30. Gillin S, Sorkin LS. Gabapentin reverses the allodynia produced by the administration of anti-GD2 ganglioside, an immunotherapeutic drug. Anesth Analg 1998;86(1):111-116.
31. Partridge BJ, Chaplan SR, Sakamoto E, Yaksh TL. Characterization of the effects of gabapentin and 3-isobutyl-g-aminobutyric acid on substance P-induced thermal hyperalgesia. Anesthesiology 1998;88: 196-205.
32. Jun JH, Yaksh TL. The effect of intrathecal gabapentin and 3-isobutyl g-aminobutyric acid on the hyperalgesia obseved after thermal injury in the rat. Anesth Analg 1998;86(2):348-352.
33. Field MJ, Holloman EF, McCleary S, Hughes J, Singh L. Evaluation of gabapentin and S-(+)-3-isobutylgaba in a rat model of postoperative pain. J Pharmacol Exp Ther 1997;282:1242-1246.
34. Shimoyama M, Shimoyama N, Inturrisi CE, Elliott KJ. Gabapentin enhances the antinociceptive effects of spinal morphine in the rat tail-flick test. Pain 1997;72:375-382.
35. Meltzer LT, Kinsora J. Unpublished results. 1997.
36. Welty DF, Schielke GP, Vartanian MG, Taylor CP. Gabapentin anticonvulsant action in rats: disequilibrium with peak drug concentration in plasma and brain microdialyzate. Epilepsy Res 1993;16:175-181.
37. Su TZ, Lunney E, Campbell G, Oxender DL. Transport of gabapentin, a gamma-amino acid drug, by system 1 alpha-amino acid transporters: a comparative study in astrocytes, synaptosomes, and CHO cells. J Neurochem 1995;64:2125-2131.
38. Hengy H, Koelle EU. Determination of gabapentin in plasma and urine by high-performance liquid chromatography and pre-column labeling for ultraviolet detection. J Chromatogr 1985;341:473-478
39. Hooper WD, Kavanagh MC, Dickinson RG. Determination of gabapentin in plasma and urine by capillary column gas chromatography. J Chromatogr 1990;529:167-174.
40. Vollmer KO, Anhut H, Thomann P, Wagner F, Jahnchen D. Pharmacokinetic model and absolute bioavailability of the new anticonvulsant Gabapentin. Advances in Epileptology 1989;17:209-211.
41. Vollmer KO, Turck D, Wagner F, Jahnchen E, Anhut H, Thomann P. Multiple-dose pharmacokinetics of the new anticonvulsant Gabapentin. Eur J Clin Pharmacol 1989;36: Suppl.A310.
42. Stewart BH, Kugler AR, Thompson PR, Bockbrader HN. A saturable transport mechanism in the intestinal absorption of gabapentin is the underlying cause of the luck of proportionality between increasing dose and drug levels in plasma. Pharm Res 1993;10:276-281.
43. UK Gabapentin Study Group. Gabapentin in partial epilepsy. Lancet 1990;335:1114-1117.
44. The US Gabapentin Study Group No. 5. Gabapentin as add-on therapy in refractory partial epilepsy: a double-blind, placebo-controlled, parallel-group study. Neurology 1993;43:2292-2298.
45. The US Gabapentin Study Group. The long-term safety and efficacy of gabapentin (Neurontin) as add-on therapy in drug-resistant partial epilepsy. Epilepsy Res 1994;18:67-73.
46. Anhut H, Ashman P, Feuerstein TJ, Sauermunn W, Saunders M, Schmidt B. The International Gabapentin Study Group. Gabapentin (Neurontin) as add-on therapy in patients with partial seizures: a double-blind, placebo-controlled study. Epilepsia 1994;35:795-801.
47. Morris GL, 3rd. Efficacy and tolerability of gabapentin in clinical practice. Clin Ther 1995;17:891-900.
48. Chadwick D, Leiderman DB, Sauermann W, Alexander J. Garofalo E. Gabapentin in generalized seizures. Epilepsy Res 1996;25:191-197.
49. Baulac M, Cavalcanti D, Semah F, Arzimanoglou A, Portal JJ, The French Gabapentin Collaborative Group. Gabapentin add-on therapy with adaptable dosages in 610 patients with partial epilepsy: an open, observational study. Seizure 1998;7:5.5-62.
50. Bruni J. Outcome evaluation of gabapentin as add-on therapy for partial seizures. "NEON" Study Investigators Group. Neurontin Evaluation of Outcomes in Neurological Practice. Can J Neurol Sci 1998;25: 134-140.
51. Beydoun A. Monotherapy trials of new antiepileptic drugs. Epilepsia 1997;38 Suppl 9: S21-S31.
52. Bergey GK, Morris HH, Rosenfeld W, Blume WT, Penovich PE, Morrell MJ, Leiderman DB, Crockatt JG, LaMoreaux L, Garofalo E, Pierce M. Gabapentin monotherapy: I. An 8-day, double-blind, dose-controlled, multicenter study in hospitalized patients with refractory complex partial or secondarily generalized seizures. Neurology 1997;49:739-745.
53. Beydoun A, Fischer J, Labar DR, Harden C, Cantrell D, Uthman BM, Sackellares JC, Abou-Khalil B, Ramsay RE, Hayes A, Greiner M, Garofalo E, Pierce M. Gabapentin monotherapy: II. A 26-week, double-blind, dose-controlled, multicenter study of conversion from polytherapy in outpatients with refractory complex partial or secondarily generalized seizures. Neurology 1997;49:746-752.
54. Beydoun A, Fakhoury T, Nasreddine W, Abou-Khalil B. Conversion to high-dose gabapentin monotherapy in patients with medically refractory partial epilepsy. Epilepsia 1998;39:188-193.
55. Miller RG, Moore D, Young LA, Armon C, Barohn RJ, Bromberg MB, Bryan WW, Gelinas DF, Mendoza MC, Neville HE, Parry GJ, Petajan JH, Ravits JM, Ringel SP, Ross MA. Placebo-controlled trial of gabapentin in patients with amyotrophic lateral sclerosis. WALS Study Group. Western Amyotrophic Lateral Sclerosis Study Group. Neurology 1996;47:1383-1388.
56. Rosenberg JM, Harrell C, Ristic H, Werner RA, de Rosayro AM. The effect of gabapentin on neuropathic pain. Clin J Pain 1997;13:251-255.
57. Sist TC, Filadora VA II, Miner M, Lema M. Experience with gabapentin for neuropathic pain in the head and neck: report of ten cases. Reg Anesth 1997;22:473-478.
58. Priebe MM, Sherwood AM, Graves DE, Mueller M, Olson WH. Effectiveness of gabapentin in controlling spasiticity: a quantitative study. Spinal Cord 1997;35:171-175.
59. Gruenthal M, Mueller M, Olson WL, Priebe MM, Sherwood AM, Olson WH. Gabapentin for the treatment of spasticity in patients with spinal cord injury. Spinal Cord 1997;35:686-689.
60. Adler CH. Treatment of restless legs syndrome with gabapentin. Clin Neuropharmacol 1997;20:148-151.
61. Mueller ME, Gruenthal M, Olson WL, Olson WH. Gabapentin for relief of upper motor neuron symptoms in multiple sclerosis. Arch Phys Med Rehabil 1997;78:521-524.
62. Houtchens MK, Richert JR, Sami A. Rose JW. Open label gabapentin treatment for pain in multiple sclerosis. Mult Scler 1997;3:250-253.
63. Averbuch-Heller L, Tusa RJ, Fuhry L, Rottach KG, Ganser GL, Heide W, Buttner U, Leigh RJ. A double-blind controlled study of gabapentin and baclofen as treatment for acquired nystagmus. Ann Neurol 1997;41:818-825.
64. Olson WL, Gruenthal M, Mueller ME, Olson WH. Gabapentin for parkinsonism: a double-blind, placebo-controlled, crossover trial. Am J Med 1997;102:60-66.
65. Backonja M, Beydoun A, Edwards KR, Schwanz SL, Fonseca V, Hes M, LaMoreaux L, Garofalo E. Gabapentin monotherapy for the symptomatic treatment of painful neuropathy: a multicentre, double-blind, placebo-controlled trial in patients with diabetes mellitus. J Am Med Assoc. In press.
66. Dimond KR, Pande AC, Lamoreaux L, Pierce MW. Effect of gabapentin (neurotonin) on mood and well-being in patients with epilepsy. Prog Neuro-Psychopharmacol Biol Psychiatry 1996; 20:407-417.
67. Pande AC, Davidson JRT, Greist JH, Jefferson JW, Weisler R, Sutherlan S. A Placebo-Controlled Study of Gabapentin in Social Phobia. Abs 36th Amer Coll Neuropsychopharm 1997;141.
68. McElroy SL, Soutullo CA, Keck Jr PE, Kmetz GF. A pilot trial of adjunclive gabapentin in the treatment of bipolar disorder. Ann Clin Psychiatry 1997;9:99-103.
69. McGraw T, Kosek P. Erythromelalgia pain managed with gabapentin. Anesthesiology 1997;86:988-990.
70. Zapp JJ. Postpoliomyelitis pain treated with gabapentin [letter]. Am Fam Physician 1996;53:2442-2445.
71. Sist T, Filadora V, Miner M, Lema M. Gabapentin for idiopathic trigeminal neuralgia: report of two cases. Neurology 1997;48:1467.
72. Rowbotham M, Harden N, Stacey B, Podolnick P, Magnus-Miller L. Gabapentin for the treatment of post-herpetic neuralgia: a multicentre, double-blind, placebo-controlled study. J Am Med Assoc. In press.
73. Andruszkiewicz RS, Silverman RB. A convenient synthesis of 3-alkyl-4-aminobutanoic acids. Synthesis 1989;953-955.
74. Silverman RBA, Andruszkiewicz R, Nanavanti SM, Taylor CP, Vartanian, MG. 3-alkyl-4-aminobutyric acids: the first class of anticonvulsant agents that activates L-glutamic acid decarboxylase. J Med Chem 1991;34:2295-2298.
75. Taylor CP, Vartanian MG, Andruszkiewieicz R, Silverman RB. 3-alkyl GABA and 3-alkylglutamic acid analogues: two new classes of anticonvulsant agents. Epilepsy Res 1992;11:103-110.
76. Yuen PW, Kanter GD, Taylor CP, Vartanian MG. Enantioselective synthesis of PD144723: a potent stereospecific anticonvulsant. Bioorg Med Chem Lett 1994;4:823-826.
77. Hoekstra MS, Sobieray DM, Schwindt MA, Mulhern TA, Grote TM, Huckabee BK, Hendrickson VS, Franklin LC, Granger EJ, Karrick GL. Chemical development of CI-1008. an enantiomerically pure anticonvulsant. Org Process Res Dev 1997;1:26-38.
78. Taylor CP, Vartanian MG, Yuen PW, Bigge C, Suman-Chauhan N, Hill DR. Potent and stereospecific anticonvulsant activity of 3-isobutyl GABA relates to in vitro binding at a novel site labeled by tritiated gabapentin. Epilepsy Res 1993;14:11-15.
79. Taylor CP, Vartanian MG. Profile of anticonvulsant activity of CI-1008 (Pregabalin) in animal models. Epilepsia 1997;38(Suppl. 8):35.
80. Williamson J, Lothman CTE, Bertram E. Comparison of S-(+)-3 Isobutyl GABA and Gabapentin against kindled hippocampal seizures. Epilepsia 1997;38(Suppl. 8):29.
81. Houghton AK, Lu Y, Westlund KN. S-(+)-3-isobutylgaba and its stereoisomer reduces the amount of inflammation and hyperalgesia in an acute arthritis model in the rat. J Pharmacol Exp Ther 1998;285:533-538.
82. Vartanian MG, Taylor CP, Bartoszyk GD. Unpublished results. 1991.
83. 3H]gabapentin binding to a novel site in rat brain: homogenate binding studies. Eur J Pharmacol 1993;244:293-301.
84. Satzinger G, Hartenstein J, Fritschi E, Vigelius WD. Cycloaliphatic aminosulfonic acid derivatives and pharmaceutical preparations for combating heart and vascular diseases. EP 133318. 1985.
85. Gee NS, Brown JP, Dissanayake VUK, Offord J, Thurlow R, Woodruff GN. The novel anticonvulsant drug, gabapentin (Neurontin), binds to the α2δ subunit of a calcium channel. J Biol Chem 1996;271:5768-5776.
86. Bryans JS, Davies N, Gee NS, Horwell DC, Kneen CO, Morrell AI, O'Neill JA, Ratcliffe GS. Investigation into the preferred conformation of gabapentin for interaction with its binding site on the α2δ subunit of a calcium channel. Bioorg Med Chem Lett 1997;7:2481-2484.
87. Bryans JS, Davies N, Gee NS, Dissanayake VU, Ratcliffe GS, Horwell DC, Kneen CO, Morrell AI, Oles RJ, O'Toole JC, Perkins GM, Singh L, Suman Chauhan N, O'Neil JA. Identification of novel ligands for the gabapentin binding site on the α2δ subunit of a calcium channel and their evaluation as anticonvulsant agents. J Med Chem 1998;41:1838-1845.
88. Bryans J, Horwell DC, Kneen CO, Morrell AI, Ratcliffe GS, Hartenstein J. Novel substituted cyclic amino acids related to Gabapentin and their use as anti-epileptic, anxiolytic and analgesic agents. PCT Int Appl WO 9733858. 1997.
89. Bryans JS, Horwell DC, McGuffog J, Morrell AI, O'Niell JA, Ratcliffe GS. Bioactive conformations of the ligands for the calcium channel α2δ Gabapentin binding site. Med Chem Res 1998;8:153-162.
90. Horwell DC, Bryans JS, Kneen CO, Morrell AI, Ratcliffe GS. Preparation of novel bridged cyclic amino acids as pharmaceutical agents. WO 9733859. 1997.
91. Horwell DC, Bryans JS, Kneen CO, Ratcliffe GS. Preparation of 4-(aminomethyl)tetrahydro(thio)pyran-4-ylacetic acid derivatives as nervous system agents.WO 9729101. 1997.
92. Serfass L, Casara PJ, General synthesis of 3-substituted alkenyl GABA as potential anticonvulsants. Bioorg Med Chem Lett 1998;8:2599-2602.
93. Taylor CP. Gabapentin: Mechanisms of action. In: Levy RH, Mattson RH, Meldrum BS, editors. Antiepileptic drugs. New York: Raven Press: 1995. p 829-841.
94. Goldlust A, Su T-Z, Welty DF, Taylor CP, Oxender DL. Effects of anticonvulsant drug gabapentin on the enzymes in metabolic pathways of glutamate and GABA. Epilepsy Res 1995;22:1-11.
95. Loscher W, Honack D, Taylor CP. Gabapentin increases aminooxyacetic acid-induced GABA accumulation in several regions of rat brain. Neurosci Lett 1991;128:150-154.
96. Leach JP, Sills GJ, Butler E, Forrest G, Thompson GG, Brodie MJ. Neurochemical actions of gabapentin in mouse brain. Epilepsy Res 1997;27:175-180.
97. Petroff OAC, Rothman DL, Behar KL, Lamoureux D, Mattson RH. The effect of gabapentin on brain gamma-aminobutyric acid in patients with epilepsy. Ann Neurol 1996;39:95-99.
98. Mattson RH, Rothman DL, Behar KL, Petroff OAC, Gabapentin: a GABA active drug. Epilepsia 1997; 38:65-66.
99. Gotz E, Feuerstein TJ, Lais A, Meyer DK. Effects of gabapentin on release of gamma-aminobutyric acid from slices of rat neostriatum. Arzneimittelforschung 1993;43:636-638.
100. Kocsis JD, Honmou O. Gabapentin increases GABA-induced depolarization in rat neonatal optic nerve. Neurosci Lett 1994;169:181-184.
101. Honmou O, Oyelese AA, Kocsis JD. The anticonvulsant gabapentin enhances promoted release of GABA in hippocampus: a field potential analysis. Brain Res 1995;692:273-277.
102. Honmou O, Kocsis JD, Richerson GB. Gabapentin potentiates the conductance increase induced by nipecotic acid in CA1 pyramidal neurons in vitro. Epilepsy Res 1995;20:193-202.
103. Xiong Z-Q, Stringer JL. Effects of felbamate, gabapentin and lamotrigine on seizure parameters and excitability in the rat hippocampus. Epilepsy Res 1997;27:187-194.
104. Fichter N, Taylor CP, Feuerstein TJ. Nipecotate-induced GABA release from slices of the rat caudatoputamen: effects of Gabapentin. Arch Pharmacol 1996;354:R35.
105. Petroff OAC, Manor D, Behar KL. Gabapentin decreases coritical glutamate rapidly in a rat model. Epilepsy Res. In press.
106. Yudkoff M. Brain metabolism of branched-chain amino acids. Glia 1997;21:92-98.
107. Kanamori K, Ross BD, Kondrat RW. Rate of glutamate synthesis from leucine in rat brain measured in vivo by 15N NMR. J Neurochem 1998;70:1304-1315.
108. Hutson SM, Berkich D, Drown P, Xu B, Aschner M, LaNoue KF. Role of branched-chain aminotransferase isoenzymes and gabapentin in neurotransmitter metabolism. J Neurochem 1998;71:863-874.
109. Welty DF, Schielke GP, Rothstein JD. Potential treatment of amyotrophic lateral sclerosis with gabapentin: a hypothesis. Ann Pharmacother 1995;29:1164-1167.
110. Bloms-Funke P, Loescher W. The anticonvulsant gabapentin decreases firing rates of substantia nigra pars reticulata neurons. Eur J Pharmacol 1996;316:211-218.
111. 2+ channels: role in channel function. Trends in Neurosci 1998;21:148-154.
112. Rock DM, Kelly KM, Macdonald RL. Gabapentin action on ligand- and voltage-gated responses in cultured rodent neurons. Epilepsy Res 1993;16:89-98.
113. Stefani A, Spadoni F, Bernardi G. Gabapentin inhibits calcium currents in isolated rat brain neurons. Neuropharmacology 1998;37:83-91.
114. Wamil AW, McLean MJ. Limitation by gabapentin of high frequency action potential firing by mouse central neurons in cell culture. Epilepsy Res 1994;17:1-11.
115. Schlicker E, Reimann W, Goetherl M. Gabapentin decreases monoamine release without affecting acetylcholine release in the brain. Arzneim-Forsch 1985;35:1347-1349.
116. Reimann W. Inhibition by GABA, baclofen and gabapentin of dopamine release from rabbit caudate nucleus: are there common or different sites of action? Eur J Pharmacol 1983;94:341-344.
117. Pugsley TA, Whetzel SZ, Dooley DJ. Reduction odf 3,4-diaminopyridine-induced biogenic amine synthesis and release in rat brain by gabapentin. Psychopharmacology 1998;137:74-80.
118. Rao ML, Clarenbach P, Vahlensieck M, Kraetzschmar S. Gabapentin augments whole blood serotonin in healthy young men. J Neural Transm 1988;73:129-134.