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508 Antiepileptics 2. Kirov G, Tredget J. Add-on topiramate reduces weight in overweight Valpromide (rINN) patients with affective disorders: a clinical case series. BMC Psychi- Valproate atry 2005; 5: 19. Available at: http://www.biomedcentral.com/ Valproato. Dipropilacetamida; Dipropylacetamide; Valpromida; Valpromi- content/pdf/1471-244X-5-19.pdf (accessed 09/06/08) dum. 2-Propylvaleramide. 3. Khazaal Y, et al. Long-term topiramate treatment of psychotrop- Вальпроат ic drug-induced weight gain: a retrospective chart review. Gen Вальпромид Hosp Psychiatry 2007; 29: 446–9. NOTE. Valproate is a generic term applied to valproic acid and its salts and esters. C8H17NO = 143.2. 4. Eliasson B, et al. Weight loss and metabolic effects of topiramate CAS — 2430-27-5. in overweight and obese type 2 diabetic patients: randomized ATC — N03AG02. double-blind placebo-controlled trial. Int J Obes 2007; 31: Valproic Acid (BAN, USAN, rINN) 1140–7. ATC Vet — QN03AG02. Abbott-44089; Acide valproïque; Ácido dipropilacético; Ácido Psychiatric disorders. Topiramate has been tried in several valproico; Acidum valproicum; Kyselina valproová; Valproiinihap- 1 _ Adverse Effects psychiatric disorders, including schizophrenia (p.955), dis- po; Valproik Asit; Valproine˙ rugštis; Valproinsav; Valproinsyra. 2- turbed behaviour2 (p.954), post-traumatic stress disorder3 Propylvaleric acid; 2-Propylpentanoic acid. The most frequently reported adverse effects associat- (p.953), and social anxiety disorder4 (see Phobic Disorders, ed with valproate therapy are gastrointestinal distur- 5-7 Вальпроевая Кислота p.953). It has also been tried in binge eating. For its use in bi- bances, particularly at the start of therapy; enteric-coat- polar disorder see above. C8H16O2 = 144.2. 1. Tiihonen J, et al. Topiramate add-on in treatment-resistant schiz- CAS — 99-66-1. ed formulations, taking doses with meals, and starting ophrenia: a randomized, double-blind, placebo-controlled, ATC — N03AG01. with low doses may minimise symptoms. There may crossover trial. J Clin Psychiatry 2005; 66: 1012–15. ATC Vet — QN03AG01. be increased appetite, and weight gain is common. 2. Nickel MK, et al. Topiramate treatment of aggression in female borderline personality disorder patients: a double-blind, place- Less common adverse effects include oedema, head- bo-controlled study. J Clin Psychiatry 2004; 65: 1515–19. ache, reversible prolongation of bleeding time, and 3. Berlant JL. Prospective open-label study of add-on and mono- H3C therapy topiramate in civilians with chronic nonhallucinatory thrombocytopenia. Leucopenia and bone marrow de- posttraumatic stress disorder. BMC Psychiatry 2004; 4: 24. OH pression have been reported. Neurological adverse ef- Available at: http://www.biomedcentral.com/content/pdf/ H3C 1471-244X-4-24.pdf (accessed 09/06/08) fects including ataxia, tremor, sedation, lethargy, con- 4. Van Ameringen M, et al. An open trial of topiramate in the treat- O fusion, and more rarely encephalopathy and coma, ment of generalized social phobia. J Clin Psychiatry 2004; 65: have occasionally been reported, although these are of- 1674–8. Pharmacopoeias. In Eur. (see p.vii) and US. 5. Nickel C, et al. Topiramate treatment in bulimia nervosa pa- ten associated with too high a starting dose, increasing tients: a randomized, double-blind, placebo-controlled trial. Int J Ph. Eur. 6.2 (Valproic Acid). A colourless or very slightly yel- Eat Disord 2005; 38: 295–300. low, slightly viscous, clear liquid. Very slightly soluble in water; doses too rapidly, or use with other antiepileptics. Very 6. Tata AL, Kockler DR. Topiramate for binge-eating disorder as- miscible with alcohol and with dichloromethane. It dissolves in rare cases of extrapyramidal symptoms or reversible sociated with obesity. Ann Pharmacother 2006; 40: 1993–7. dilute solutions of alkali hydroxides. Store in airtight containers. dementia associated with cerebral atrophy have been 7. Claudino AM, et al. Double-blind, randomized, placebo-control- USP 31 (Valproic Acid). A colourless to pale yellow, slightly vis- reported. Increased alertness may occur, which is gen- led trial of topiramate plus cognitive-behavior therapy in binge- cous, clear liquid having a characteristic odour. Slightly soluble eating disorder. J Clin Psychiatry 2007; 68: 1324–32. erally considered beneficial, but occasionally aggres- in water; freely soluble in alcohol, in acetone, in chloroform, in Tremor. A beta blocker is often the first drug used in patients ether, in methyl alcohol, in benzene, in n-heptane, and in 1N sion, hyperactivity, and behavioural disturbances have with essential tremor who require regular treatment (p.1231); sodium hydroxide; slightly soluble in 0.1N hydrochloric acid. been reported. Hearing loss has been noted. There may 1,2 however, topiramate has also been tried. Store in airtight glass, stainless steel, or polyethylene containers. occasionally be rashes, and, rarely, hirsutism, acne, 1. Galvez-Jimenez N, Hargreave M. Topiramate and essential trem- or. Ann Neurol 2000; 47: 837–8. toxic epidermal necrolysis and Stevens-Johnson syn- 2. Ondo WG, et al. Topiramate in essential tremor: a double-blind, Sodium Valproate (BANM, rINNM) drome or erythema multiforme. Transient hair loss, placebo-controlled trial. Neurology 2006; 66: 672–7. Abbott-44090; Natrii valproas; Natrio valproatas; Natriumval- sometimes with regrowth of curly hair, has occurred. Preparations proaatti; Natriumvalproat; Nátrium-valproát; Natrium-valproát; Irregular periods, amenorrhoea, and gynaecomastia NIK-240; Sodium, valproate de; Sodyum Valproat; Valproate de Proprietary Preparations (details are given in Part 3) have been reported rarely. Arg.: Neutop; Topamac; Topictal; Topirex; Austral.: To p a m a x ; Austria: Sodium; Valproate Sodium (USAN); Valproato sódico. Sodium 2- To p a m a x ; Belg.: To p a m a x ; Braz.: To p a m a x ; Canad.: To p a m a x ; Chile: propylvalerate; Sodium 2-propylpentanoate. Liver dysfunction including hepatic failure has occa- Topamax; Toprel; Cz.: To p a m a x ; To p i r a g i s ; Denm.: Epitomax; Topimax; Натрий Вальпроат sionally been reported, usually in the first few months Fin.: To p i m a x ; Fr.: Epitomax; Ger.: To p am ax ; Gr.: To p a m a c ; Hong Kong: To p a m a x ; Hung.: To p a m a x ; India: To p a m a c ; To p a m a t e ; Indon.: To p a m ax ; C8H15NaO2 = 166.2. of treatment, and requires valproate withdrawal; there Irl.: Topamax; Israel: Topamax; Ital.: Topamax; Malaysia: To p a m a x ; CAS — 1069-66-5. have been fatalities. Elevation of liver enzyme values Mex.: To p a m a x ; Neth.: Epitomax; Topamax; Norw.: To p i m a x ; NZ: ATC — N03AG01. is common but normally transient and dose-related. To p a m a x ; Philipp.: Topamax; Pol.: To p a m a x ; Port.: To p a m ax ; To p t r i x ; ATC Vet — QN03AG01. Rus.: To p a m a x ( Топамакс); S.Afr.: To p a m a x ; Singapore: To p a m a x ; Hyperammonaemia has occurred, even in the absence Spain: Bipomax; Topamax; Swed.: Topimax; Switz.: Topamax; Thai.: Pharmacopoeias. In Chin., Eur. (see p.vii), Int., Jpn., and US. of overt hepatic failure, and is sometimes associated To p a m a x ; Turk.: To p a m a x ; UK: To pa m ax ; USA: To p a m a x ; Venez.: Ph. Eur. 6.2 (Sodium Valproate). A white or almost white, hy- To p a m a x . groscopic, crystalline powder. Very soluble in water; slightly to with neurological symptoms; hyperglycinaemia has freely soluble in alcohol. Store in airtight containers. also been reported. Pancreatitis has also been reported USP 31 (Divalproex Sodium). A white to off-white powder. Sol- rarely, and fatalities have occurred; plasma amylase Trimethadione (BAN, rINN) uble in acetone; practically insoluble in acetonitrile; very soluble should be measured if there is acute abdominal pain, Trimetadion; Trimetadiona; Trimetadionas; Trimetadioni; Tri- in chloroform; freely soluble in ethyl ether and in methyl alcohol. Store in airtight containers. although the value of serum amylase as a diagnostic methadion; Triméthadione; Trimethadionum; Trimethinum; tool has been questioned—see Effects on the Pancreas, Troxidone. 3,5,5-Trimethyl-1,3-oxazolidine-2,4-dione. Valproate Pivoxil (rINN) below. In a few patients there have been reports of re- Триметадион CHF-1504; Valproato de pivoxilo; Valproato pivoxilo; Val- versible defects in renal tubular function (Fanconi’s C6H9NO3 = 143.1. syndrome). CAS — 127-48-0. proatum Pivoxilum. Hydroxymethyl 2-propylvalerate pivalate. ATC — N03AC02. Вальпроат Пивоксил Congenital malformations have been reported in ATC Vet — QN03AC02. C14H26O4 = 258.4. infants born to women who had received antiepileptics CAS — 77372-61-3. including valproate during pregnancy. ATC — N03AG01. H3C O ATC Vet — QN03AG01. Inflammatory reactions and pain have been reported at O the injection site after intravenous doses. H C 3 Valproate Semisodium (rINN) N Incidence of adverse effects. Adverse effects were present in Abbott-50711; Divalproex Sodium (USAN); Semisodium Val- 71 of 88 children receiving sodium valproate monotherapy1 and, O CH 3 proate (BAN); Valproate Semisodique; Valproato semisódico; Val- although average doses in these patients were significantly high- proatum Seminatricum. 2-Propylvaleric acid—Sodium 2-propyl- er than in the 17 with no adverse effects, no difference in the plas- Pharmacopoeias. In Eur. (see p.vii), Int., and Jpn. valerate (1:1); Sodium hydrogen bis(2-propylvalerate) oligomer. ma concentrations was observed between the 2 groups. Ph. Eur. 6.2 (Trimethadione). Colourless or almost colourless crystals. Soluble in water; very soluble in alcohol. Protect from Вальпроат Семинатрий • Behavioural alterations seen in 56 included irritability, longer and deeper sleep, superficial sleep, hyperactivity, being more light. C16H31NaO4 = 310.4. CAS — 76584-70-8. alert, lassitude, drowsiness, being more sociable, calmness, Profile ATC — N03AG01. being happier, absent mindedness, being sadder, aggressive- Trimethadione is an oxazolidinedione antiepileptic that has been ATC Vet — QN03AG01. ness, being more skillful, and docility; it was emphasised that given in the treatment of absence seizures refractory to other an- stimulatory reactions were as frequent as depressant effects tiepileptics.
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  • Comparison of the Effects of Zonisamide, Ethosuximide and Pregabalin in the Chronic Constriction Injury Induced Neuropathic Pain in Rats

    Comparison of the Effects of Zonisamide, Ethosuximide and Pregabalin in the Chronic Constriction Injury Induced Neuropathic Pain in Rats

    [Downloaded free from http://www.amhsr.org] Original Article Comparison of the Effects of Zonisamide, Ethosuximide and Pregabalin in the Chronic Constriction Injury Induced Neuropathic Pain in Rats Goyal S, Singla S, Kumar D, Menaria G Department of Pharmacology, Pacific College of Pharmacy, Pacific University, Udaipur, Rajasthan, India Address for correspondence: Dr. Sachin Goyal, Abstract Department of Pharmacology, Background: Evidence has been generated that various anticonvulsant agents provide relief Pacific College of Pharmacy, Pacific University, of several chronic pain syndromes and therefore as an alternative to opioids, nonsteroidal Udaipur ‑ 313 024, Rajasthan, India. anti‑inflammatory, and tricyclic antidepressant drugs in the treatment of neuropathic pain. The E‑mail: [email protected] results of these studies thus raise the question of whether all anticonvulsant drugs or particular mechanistic classes may be efficacious in the treatment of neuropathic pain syndromes. Aim: The aim was to compare the clinically used anticonvulsant drugs which are differ in their mechanism of action in a chronic pain model, the chronic constriction injury, in order to determine if all anticonvulsants or only particular mechanistic classes of anticonvulsants are analgesic. Materials and Methods: The study included zonisamide, ethosuximide and pregabalin. All compounds were anticonvulsant with diverse mechanism of actions. The peripheral neuropathic pain was induced by chronic constriction injury of the sciatic nerve in male Sprague‑Dawley rats. Zonisamide (80 and 40 mg/kg), ethosuximide (300 and 100 mg/kg), pregabalin (50 and 20 mg/kg), and saline was administered intraperitoneally in respective groups in a blinded, randomized manner from postoperative day (POD) 7‑13. Paw withdrawal duration to spontaneous pain, chemical allodynia and mechanical hyperalgesia and paw withdrawal latency to mechanical allodynia and thermal hyperalgesia were tested before drug administration on POD7 and after administration on POD 7, 9, 11 and 13.
  • Center for Drug Evaluation and Research

    Center for Drug Evaluation and Research

    CENTER FOR DRUG EVALUATION AND RESEARCH APPLICATION NUMBER: 22-006 PHARMACOLOGY REVIEW(S) Tertiary Pharmacology Review By: Paul C. Brown, Ph.D., ODE Associate Director for Pharmacology and Toxicology OND IO NDA: 20-427 and 22-006 Submission date: December 28, 2007 (Complete response) Drug: vigabatrin Sponsor: Ovation Pharmaceuticals Indication: 20-427: refractory complex partial seizures in adults 22-006: infantile spasms Reviewing Division: Division of Neurology Products Introductory Comments: The regulatory history of these two NDAs is summarized in the supervisory pharm/tox review. The pharm/tox review of NDA 20-427 found the nonclinical information adequate to support approval. The pharm/tox reviewer for NDA 22-006 did not find the nonclinical information adequate to support approval primarily based on evidence that juvenile animals were sensitive to neurotoxic effects of vigabatrin. The pharm/tox supervisor recognized this concern but did not object to the approval of NDA 22-006 based on the clinical benefit of vigabatrin in infantile spasms which is a serious indication with no other approved therapy. The supervisor recommended that additional studies on the retinal damage and neurotoxicity induced by vigabatrin be conducted as postmarketing requirements. This includes the following studies: 1. A toxicology study in the juvenile rat examining the potential of vigabatrin exposure during development to produce neuronal damage. 2. A juvenile animal toxicology study of vigabatrin in a non-rodent species. 3. A study examining the effect of taurine on vigabatrin-induced retinal damage in rodent. Conclusions: I have discussed these NDAs with the division pharm/tox supervisor and agree that they may be approved from a pharm/tox perspective.