gamma-aminobutyric acid and Abnormalities, Drug-Induced studies

gamma-Aminobutyric Acid: The most common inhibitory neurotransmitter in the central nervous system.
gamma-aminobutyric acid : A gamma-amino acid that is butanoic acid with the amino substituent located at C-4.

Abnormalities, Drug-Induced: Congenital abnormalities caused by medicinal substances or drugs of abuse given to or taken by the mother, or to which she is inadvertently exposed during the manufacture of such substances. The concept excludes abnormalities resulting from exposure to non-medicinal chemicals in the environment.

Research Excerpts

Excerpt	Relevance	Reference
"Our objectives were to 1) determine whether first-trimester use of gabapentin is associated with an increased risk for major malformations; 2) examine rates of spontaneous abortions, therapeutic abortions, stillbirths, mean birth weight and gestational age at delivery; and 3) examine rates of poor neonatal adaptation syndrome following late pregnancy exposure."	9.17	Pregnancy outcomes following gabapentin use: results of a prospective comparative cohort study. ( Bernard, N; Einarson, A; Einarson, TR; Etwell, F; Fujii, H; Goel, A; Han, JY; Koren, G; Matsui, D; Pistelli, A; Stephens, S; Yates, LM, 2013)
"We have data on 223 pregnancy outcomes exposed to gabapentin and 223 unexposed pregnancies."	9.17	Pregnancy outcomes following gabapentin use: results of a prospective comparative cohort study. ( Bernard, N; Einarson, A; Einarson, TR; Etwell, F; Fujii, H; Goel, A; Han, JY; Koren, G; Matsui, D; Pistelli, A; Stephens, S; Yates, LM, 2013)
"Our results suggest that although this sample size is not large enough to make any definitive conclusions, and there was no comparator group treated with other antiepileptic drugs, gabapentin use in pregnancy does not appear to increase the risk for major malformations."	9.17	Pregnancy outcomes following gabapentin use: results of a prospective comparative cohort study. ( Bernard, N; Einarson, A; Einarson, TR; Etwell, F; Fujii, H; Goel, A; Han, JY; Koren, G; Matsui, D; Pistelli, A; Stephens, S; Yates, LM, 2013)
"Our objectives were to 1) determine whether first-trimester use of gabapentin is associated with an increased risk for major malformations; 2) examine rates of spontaneous abortions, therapeutic abortions, stillbirths, mean birth weight and gestational age at delivery; and 3) examine rates of poor neonatal adaptation syndrome following late pregnancy exposure."	5.17	Pregnancy outcomes following gabapentin use: results of a prospective comparative cohort study. ( Bernard, N; Einarson, A; Einarson, TR; Etwell, F; Fujii, H; Goel, A; Han, JY; Koren, G; Matsui, D; Pistelli, A; Stephens, S; Yates, LM, 2013)
"We have data on 223 pregnancy outcomes exposed to gabapentin and 223 unexposed pregnancies."	5.17	Pregnancy outcomes following gabapentin use: results of a prospective comparative cohort study. ( Bernard, N; Einarson, A; Einarson, TR; Etwell, F; Fujii, H; Goel, A; Han, JY; Koren, G; Matsui, D; Pistelli, A; Stephens, S; Yates, LM, 2013)
"Our results suggest that although this sample size is not large enough to make any definitive conclusions, and there was no comparator group treated with other antiepileptic drugs, gabapentin use in pregnancy does not appear to increase the risk for major malformations."	5.17	Pregnancy outcomes following gabapentin use: results of a prospective comparative cohort study. ( Bernard, N; Einarson, A; Einarson, TR; Etwell, F; Fujii, H; Goel, A; Han, JY; Koren, G; Matsui, D; Pistelli, A; Stephens, S; Yates, LM, 2013)
" More specifically, vigabatrin, which is a very useful and well tolerated new antiepileptic drug for refractory partial epilepsy, should be started at a low dosage of 0."	4.79	The new anticonvulsant drugs. Implications for avoidance of adverse effects. ( Krämer, G; Schmidt, D, 1994)
" By contrast, offspring of rats exposed to carbamazepine (which at the dose used produced low plasma concentrations) or to generalized convulsive seizures showed no clear-cut evidence of dysplasias."	3.74	Fetal exposure to GABA-acting antiepileptic drugs generates hippocampal and cortical dysplasias. ( Ben-Ari, Y; Depaulis, A; Jorquera, I; Manent, JB; Mazzucchelli, I; Perucca, E; Represa, A, 2007)
"A total of 60 pregnant mice, divided into 12 groups of five mice each, were exposed to gabapentin in four different doses of 0 (control), 113, 226, or 452 mg/kg body weight per day, at three different gestational stages including early gestation (1-6 days), mid-gestation (7-12 days), and late gestation (13-17 days)."	3.74	Teratogenic effects of the anticonvulsant gabapentin in mice. ( Goel, RK; Madhyastha, S; Nasar, MA; Pai, MM; Prabhu, LV; Rai, R; Singh, G; Yadav, SK, 2008)
"We aim to study and elucidate the safety profile of the antiepileptic doses of gabapentin during pregnancy, and to evaluate gabapentin-induced murine fetotoxicity at different dose levels."	3.74	Teratogenic effects of the anticonvulsant gabapentin in mice. ( Goel, RK; Madhyastha, S; Nasar, MA; Pai, MM; Prabhu, LV; Rai, R; Singh, G; Yadav, SK, 2008)
"Gabapentin should not be prescribed during pregnancy, as no therapeutic dose of gabapentin is safe during this period as far as the foetal well-being is concerned."	3.74	Teratogenic effects of the anticonvulsant gabapentin in mice. ( Goel, RK; Madhyastha, S; Nasar, MA; Pai, MM; Prabhu, LV; Rai, R; Singh, G; Yadav, SK, 2008)
" In the last decade, pregnancy registries have been activated by collaborative groups of physicians in Europe (EURAP), North America (NAREP), Australia and India (the latter two recently merged into EURAP), to enroll a large number of exposed women to be monitored prospectively with standardized methods, and by three pharmaceutical companies marketing lamotrigine, gabapentin and vigabatrin, as part of their post-marketing surveillance."	3.71	Pregnancy registries in epilepsy. ( Annegers, JF; Beghi, E, 2001)
" Diazepam (Valium) could cause cleft palate by mimicking GABA."	3.67	Neuropharmacologic teratogenesis and neurotransmitter regulation of palate development. ( Zimmerman, EF, 1984)
" Diazepam may cause cleft palate by mimicking GABA."	3.67	Role of neurotransmitters and teratogens on palate development. ( Venkatasubramanian, K; Wee, EL; Zimmerman, EF, 1985)
" Finally, gabapentin is a very safe add-on medication."	2.39	The new anticonvulsant drugs. Implications for avoidance of adverse effects. ( Krämer, G; Schmidt, D, 1994)
" More specifically, vigabatrin, which is a very useful and well tolerated new antiepileptic drug for refractory partial epilepsy, should be started at a low dosage of 0."	2.39	The new anticonvulsant drugs. Implications for avoidance of adverse effects. ( Krämer, G; Schmidt, D, 1994)
"While seizures may affect adversely maternal and fetal outcome, antiepileptic drugs (AEDs) may increase the incidence of congenital abnormalities and possibly affect postnatal cognitive development in the offspring."	1.34	Fetal exposure to GABA-acting antiepileptic drugs generates hippocampal and cortical dysplasias. ( Ben-Ari, Y; Depaulis, A; Jorquera, I; Manent, JB; Mazzucchelli, I; Perucca, E; Represa, A, 2007)
"Vigabatrin (VGB) is a relatively recently introduced antiepileptic drug that enhances the brain levels of gamma aminobutyric acid (GABA)."	1.30	Teratogenic effects of vigabatrin in TO mouse fetuses. ( Abdulrazzaq, YM; Bastaki, SM; Padmanabhan, R, 1997)
"Diazepam may cause cleft palate by mimicking GABA."	1.27	Role of neurotransmitters and teratogens on palate development. ( Venkatasubramanian, K; Wee, EL; Zimmerman, EF, 1985)

Research

Studies (19)

Authors

Clinical Trials (1)

Trial Overview

Trial Outcomes

Baseline Adjusted Mean Daily Motherisk-PUQE Total Scores (Pregnancy-unique Quantification of Emesis and Nausea Scale) for Days 5-7

Timeframe	Studies, this research(%)	All Research%
pre-1990	4 (21.05)	18.7374
1990's	5 (26.32)	18.2507
2000's	5 (26.32)	29.6817
2010's	5 (26.32)	24.3611
2020's	0 (0.00)	2.80

Authors	Studies
Fujii, H	1
Goel, A	1
Bernard, N	1
Pistelli, A	1
Yates, LM	1
Stephens, S	1
Han, JY	1
Matsui, D	1
Etwell, F	1
Einarson, TR	1
Koren, G	1
Einarson, A	1
Yüksel, M	1
Sarıkaya, R	1
Bostanci, N	1
Holmes, LB	1
Hernandez-Diaz, S	1
Dolk, H	1
van den Berg, Lde J	1
Loane, M	1
Wang, H	1
Morris, J	1
Koo, J	1
Zavras, A	1
Manent, JB	1
Jorquera, I	1
Mazzucchelli, I	1
Depaulis, A	1
Perucca, E	1
Ben-Ari, Y	1
Represa, A	1
Prabhu, LV	1
Rai, R	1
Pai, MM	1
Yadav, SK	1
Madhyastha, S	1
Goel, RK	1
Singh, G	1
Nasar, MA	1
Zimmerman, EF	3
Nau, H	1
Löscher, W	2
Schmidt, D	1
Krämer, G	1
Appleton, RE	1
Abdulrazzaq, YM	1
Bastaki, SM	1
Padmanabhan, R	1
Tueth, MJ	1
Murphy, TK	1
Evans, DL	1
Iqbal, MM	1
Gundlapalli, SP	1
Ryan, WG	1
Ryals, T	1
Passman, TE	1
Beghi, E	1
Annegers, JF	1
Venkatasubramanian, K	1
Wee, EL	1

Trial	Phase	Enrollment	Study Type	Start Date	Status
Comparison of Gabapentin and Metoclopramide for Treating Hyperemesis Gravidarum[NCT02163434]	Phase 2	31 participants (Actual)	Interventional	2014-06-30	Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Score range: 6-30 with higher score indicating a worse outcome. (NCT02163434)
Timeframe: 1 week

Baseline Adjusted Mean Daily Nausea Scores From the Motherisk-PUQE for Days 5-7.

Intervention	units on a scale (Mean)
Gabapentin	6.35
Metoclopramide	13.22

Score range: 2-10 with higher score indicating a worse outcome. (NCT02163434)
Timeframe: 1 week

Baseline Adjusted Mean Daily Oral Nutrition Score for Days 5-7

Intervention	units on a scale (Mean)
Gabapentin	2.01
Metoclopramide	3.69

Score range: 0-15 with higher score indicating a better outcome. (NCT02163434)
Timeframe: 1 week

Desire to Continue Therapy at Study Endpoint

Intervention	units on a scale (Mean)
Gabapentin	7.86
Metoclopramide	4.01

Scores: 0=no, 1=yes. Thus, a higher score indicates a better outcome. (NCT02163434)
Timeframe: 1 week

Global Satisfaction of Treatment at the Study Endpoint.

Intervention	units on a scale (Mean)
Gabapentin	0.67
Metoclopramide	0.14

Score range: 0-4 with higher score indicating a better outcome. (NCT02163434)
Timeframe: 1 week

Percent of Subjects Requiring Repeat iv Hydration or Hospital Admission for HG From the Outpatient Setting.

Reviews

Trials

Other Studies

13 other studies available for gamma-aminobutyric acid and Abnormalities, Drug-Induced

Article	Year
The new anticonvulsant drugs. Implications for avoidance of adverse effects. Drug safety, 1994, Volume: 11, Issue:6 Topics: Abnormalities, Drug-Induced; Anemia, Aplastic; Anticonvulsants; Chemical and Drug Induced Liver Inju	1994
The new antiepileptic drugs. Archives of disease in childhood, 1996, Volume: 75, Issue:3 Topics: Abnormalities, Drug-Induced; Acetates; Adolescent; Adult; Amines; Anticonvulsants; Child; Child, Pre	1996
Special considerations: use of lithium in children, adolescents, and elderly populations. The Journal of clinical psychiatry, 1998, Volume: 59 Suppl 6 Topics: Abnormalities, Drug-Induced; Acetates; Adolescent; Adult; Age Factors; Aged; Amines; Anticonvulsants	1998
Effects of antimanic mood-stabilizing drugs on fetuses, neonates, and nursing infants. Southern medical journal, 2001, Volume: 94, Issue:3 Topics: Abnormalities, Drug-Induced; Acetates; Adult; Amines; Antimanic Agents; Benzodiazepines; Breast Feed	2001
Pharmacological, toxicological and neurochemical effects of delta 2(E)-valproate in animals. Pharmaceutisch weekblad. Scientific edition, 1992, Jun-19, Volume: 14, Issue:3A Topics: Abnormalities, Drug-Induced; Animals; Anticonvulsants; Brain; Fatty Acids, Monounsaturated; gamma-Am	1992

Article	Year
Genotoxic evaluation of antiepileptic drugs by Drosophila somatic mutation and recombination test. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, 2010, Volume: 48, Issue:10 Topics: Abnormalities, Drug-Induced; Amines; Animals; Anticonvulsants; Cyclohexanecarboxylic Acids; Drosophi	2010
Newer anticonvulsants: lamotrigine, topiramate and gabapentin. Birth defects research. Part A, Clinical and molecular teratology, 2012, Volume: 94, Issue:8 Topics: Abnormalities, Drug-Induced; Adult; Amines; Anticonvulsants; Case-Control Studies; Child; Child, Pre	2012
Newer anticonvulsants: lamotrigine. Birth defects research. Part A, Clinical and molecular teratology, 2012, Volume: 94, Issue:11 Topics: Abnormalities, Drug-Induced; Amines; Anticonvulsants; Cleft Palate; Cyclohexanecarboxylic Acids; Fem	2012
Antiepileptic drugs (AEDs) during pregnancy and risk of congenital jaw and oral malformation. Oral diseases, 2013, Volume: 19, Issue:7 Topics: Abnormalities, Drug-Induced; Adverse Drug Reaction Reporting Systems; Amines; Anticonvulsants; Cyclo	2013
Fetal exposure to GABA-acting antiepileptic drugs generates hippocampal and cortical dysplasias. Epilepsia, 2007, Volume: 48, Issue:4 Topics: Abnormalities, Drug-Induced; Animals; Anticonvulsants; Carbamazepine; Cerebral Cortex; Female; Fetus	2007
Teratogenic effects of the anticonvulsant gabapentin in mice. Singapore medical journal, 2008, Volume: 49, Issue:1 Topics: Abnormalities, Drug-Induced; Amines; Animals; Anticonvulsants; Body Weight; Congenital Abnormalities	2008
Neuropharmacologic teratogenesis and neurotransmitter regulation of palate development. American journal of mental deficiency, 1984, Volume: 88, Issue:5 Topics: Abnormalities, Drug-Induced; Acetylcholine; Animals; Cell Movement; Cleft Palate; Diazepam; Dopamine	1984
Valproic acid and metabolites: pharmacological and toxicological studies. Epilepsia, 1984, Volume: 25 Suppl 1 Topics: Abnormalities, Drug-Induced; Animals; Brain; Chemical and Drug Induced Liver Injury; Chemical Phenom	1984
Teratogenic effects of vigabatrin in TO mouse fetuses. Teratology, 1997, Volume: 55, Issue:3 Topics: Abnormalities, Drug-Induced; Animals; Anticonvulsants; Bone and Bones; Embryo Loss; Fetal Growth Ret	1997
Valproate and other anticonvulsants for psychiatric disorders. The Medical letter on drugs and therapeutics, 2000, Dec-11, Volume: 42, Issue:1094 Topics: Abnormalities, Drug-Induced; Acetates; Adult; Amines; Anti-Anxiety Agents; Anticonvulsants; Bipolar	2000
Pregnancy registries in epilepsy. Epilepsia, 2001, Volume: 42, Issue:11 Topics: Abnormalities, Drug-Induced; Acetates; Amines; Anticonvulsants; Australia; Cross-Cultural Comparison	2001
Role of neurotransmitters in palate development and teratologic implications. Progress in clinical and biological research, 1985, Volume: 171 Topics: Abnormalities, Drug-Induced; Animals; Biological Transport, Active; Cleft Palate; Diazepam; Female;	1985
Role of neurotransmitters and teratogens on palate development. Progress in clinical and biological research, 1985, Volume: 163C Topics: Abnormalities, Drug-Induced; Animals; Cell Differentiation; Cell Movement; Cleft Palate; Diazepam; g	1985

Intervention	Participants (Count of Participants)
Gabapentin	5
Metoclopramide	5