Neurological Drug Research Articles

Do Systemic Diseases and Medications Influence Dental Implant Osseointegration and Dental Implant Health? An Umbrella Review

The aim of this umbrella review is to evaluate what are the most common medications and systemic diseases that can affect bone–implant integration, the success rate and survival rate of dental implants, peri-implant tissue health, and implant loss. Systematic reviews, with meta-analysis or not, about how systemic diseases and medications influence dental implant osseointegration, survival rate, success rate, and peri-implant diseases, published only in the English language, are electronically searched across the most important scientific databases. The present umbrella review includes eight systematic reviews, and osteoporosis and diabetes are the most investigated pathologies. Systemic diseases, such as neurologic disorders, HIV, hypothyroidism, cardiovascular diseases, and drugs, such as beta blockers, anti-hypertensives, or diuretics do not show a decreased rate of implant osseointegration. It seems that drugs, such as proton-pump inhibitors (PPIs) or serotonin reuptake inhibitors (SSRIs), negatively affect implant osseointegration. Few studies compare the effects of drugs and systemic diseases on the parameters considered in this overview. It is important to underline how the results of this review need to be validated with subsequent and more reviews.

Smart-Phone-Assisted Optical Biosensors Based on Silk-Fibroin-Decorated Reduced Graphene Oxide Quantum Dots for Fluorescent Turn-On Recognition of l-Dopa

Levodopa (l-dopa) is a gold standard neurological drug for symptomatic medication of Parkinson’s disease. The long-term use of l-dopa therapy frequently leads to l-dopa-induced dyskinesia and several other non-motor flocculants for fluctuating plasma concentration. To alleviate the adverse effect of dopamine replacement therapy, sensitive detection of l-dopa is still challenging. Therefore, this study presents a simple strategy to develop an inexpensive, easy-to-use, smartphone-based fluorescence turn-on sensory system based on the aggregation-induced emission enhancement phenomenon for instant low-level detection of l-dopa in biological samples. The sensor was fabricated using silk-fibroin-decorated reduced graphene oxide quantum dots, which exhibit a progressive increase of fluorescence intensity in the presence of l-dopa. By measuring the turn-on efficiency of the sensor in elevated concentrations of l-dopa, the limit of detection (LOD) was evaluated as 76.18 nM over a linear range of 0–35 μM. We have further designed a smartphone-based electronic device involving a 365 nm light emitting diode attached below the rare camera for capturing the change of fluorescent color of the solution during sensing. From these images, red, green, and blue values are analyzed using a mobile phone application, and the corresponding LOD was found to be 0.29 μM in a similar linear range of concentration. This simple, cost-effective, and rapid screening gadget is very demanding for on-spot detection of the analytes in remote areas where sophisticated instrumentation is not usually available.

Nanotechnology-empowered therapeutics targeting neurodegenerative diseases.

Neurodegenerative diseases are posing pressing health issues due to the high prevalence among aging populations in the 21st century. They are evidenced by the progressive loss of neuronal function, often associated with neuronal necrosis and many related devastating complications. Nevertheless, effective therapeutical strategies to treat neurodegenerative diseases remain a tremendous challenge due to the multisystemic nature and limited drug delivery to the central nervous system. As a result, there is a pressing need to develop effective alternative therapeutics to manage the progression of neurodegenerative diseases. By utilizing the functional reconstructive materials and technologies with specific targeting ability at the nanoscale level, nanotechnology-empowered medicines can transform the therapeutic paradigms of neurodegenerative diseases with minimal systemic side effects. This review outlines the current applications and progresses of the nanotechnology-enabled drug delivery systems to enhance the therapeutic efficacy in treating neurodegenerative diseases. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Neurological Disease Therapeutic Approaches and Drug Discovery > Emerging Technologies.

Antipsychotic-Induced Parkinsonism and Dyskinesia in a 43- years Old Male with Schizophrenia: Clinical Case

The development of neurological adverse drug reactions (ADRs) from the extrapyramidal system while taking antipsychotics (APs) is well known. The common forms of neurological ADRs from the side of the extrapyramidal system are AP-induced parkinsonism (AIP) with a frequency of about 36% and AP-induced tardive dyskinesia (AITD) with an incidence of about 25%. Patients with AIP and AITD make up a significant proportion of patients in psychiatric hospitals and neuropsychiatric dispensaries with AP-induced extrapyramidal disorders requiring neurological care. These ADRs make a significant contribution to the structure of the overall morbidity and mortality of the population around the world. We presented a clinical example of 43 years old male, who developed acute AIP and AITD while taking APs. This condition was resolved with amantadine 200 mg/day after several unsuccessful attempts. It is also known that the patient had a father with Parkinson's disease in his anamnesis. The patient underwent pharmacogenetic testing of SNV rs1800497 of the DRD2 gene. According to the results the patient was a homozygous carrier of the major allele. These results did not show a positive association. At the same time, such a patient needs to undergo pharmacogenetic testing using a complete genetic risk panel for developing AIP, AITD, and Parkinson's disease.

Increased Access to Immunoglobulin Replacement Therapy for Patients with Primary Immunodeficiency in Poland Based on Clinical Usage Data of Immunoglobulin G over a 5-Year Period

Owing to the rising popularity and demand for immunoglobulins (IgG), obtaining supplies and rationalizing IgG use have become challenging. Herein, IgG consumption in Poland was analyzed through total IgG use and number of patients reported to the National Health Fund between 1 January 2016 and 31 December 2020. Total IgG used within 5 years increased by 27.48%, IgG use/1000 inhabitants/year was 23.13 g (2016) and 29.61 g (2020). In 2020, 35.5 % of IgG used was for neurological conditions, 25% for primary immunodeficiencies (PID), and 39.3% for all other indications. Within 5 years, 1,121,168.75 g IgG was used in PID; the use increased by 72%, from 783 in 2016 to 1153 patients in 2020. The proportion of patients who received subcutaneous immunoglobulin (SCIG) replacement therapy (IgRT) increased to 78% (2020). Within 5 years, 1,783,534.81 g IgG was used in neurological drug programs (+42.44%) and 2,327,513.88 g (+1.25%) outside neurological indications and outside PID. The annual IgG amount decreased in adult anesthesiology and intensive care (-46%), internal medicine (-55%), pneumonology (-50%), pediatric clinical immunology (-50%), and gynecology and obstetrics (-48%) and increased in dermatology (+178%), rheumatology (+103%), and clinical transplantation (+82%). IgG use significantly increased in Poland, mostly owing to PID. Subcutaneous IgG administration is currently the most common mode of IgRT in PID patients. An increase in SCIG administration may be expected for other indications. Implementing evidence-based clinical guidelines is key to prioritizing and rationalizing IgG use for immunomodulatory indications and secondary immune deficiencies.

Neurotoxicity induced by taxane-derived drugs: analysis of the FAERS database 2017–2021

ABSTRACT Objectives Taxane‐related neurotoxicity is a frequent clinical problem but lacks postmarketing data regarding neurological disorders. This study aimed to evaluate the potential association between neurological adverse events and several taxanederived drugs via the Food and Drug Administration Adverse Event Reporting System (FAERS). Methods Disproportionality analysis was applied to data mining of the suspected cases of neurological disorders after using different taxanes based on the FAERS data from January 2017 and December 2021. We also investigated the times to onset, fatality, and hospitalization proportions of taxanerelated neurotoxicity. Results In total, 3,940 cases were screened out, which were more prevalent in elderly patients and females. Peripheral neuropathy was a common adverse event among all taxanes with relatively strong association. Generally, the median time to neurological adverse effect onset was 27 days (interquartile range, 11.0 ~ 78.0 days) following taxane regimens, and the majority of cases were detected within the first 30 days. Among cases of neurological adverse events treated with taxane, the fatality and hospitalization proportions were 6.13% and 28.63%, respectively. Conclusion By analyzing the FAERS data, we provided a detailed profile of neurotoxicity and different taxanes in detail in terms of clinical characteristics, time to onset, and patient outcomes.

Single-Nucleotide Polymorphisms as Biomarkers of Antipsychotic-Induced Akathisia: Systematic Review

Antipsychotic-induced akathisia (AIA) is a movement disorder characterized by a subjective feeling of inner restlessness or nervousness with an irresistible urge to move, resulting in repetitive movements of the limbs and torso, while taking antipsychotics (APs). In recent years, there have been some associative genetic studies of the predisposition to the development of AIA. Objective: The goal of our study was to review the results of associative genetic and genome-wide studies and to systematize and update the knowledge on the genetic predictors of AIA in patients with schizophrenia (Sch). Methods: We searched full-text publications in PubMed, Web of Science, Springer, Google Scholar, and e-Library databases from 1977 to 2022. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) quality scale was used for the critical selection of the studies. Results: We identified 37 articles, of which 3 were included in the review. Thus, the C allele of rs1800498 (59414 C>T) and the A allele of rs1800497 (17316 G>A) (TaqIA) from the DRD2 gene as well as the TT genotype rs13212041 (77461407 C>T) from the HTR1B gene were found to be associated with AIA. Conclusions: Uncovering the genetic biomarkers of AIA may provide a key to developing a strategy for the personalized prevention and treatment of this adverse neurological drug reaction of APs in patients with Sch in real clinical practice.

Orphan Drugs in Neurology-A Narrative Review.

Orphan diseases, or rare diseases, are defined in Europe as diseases that affect less than 5 out of every 10,000 citizens. Given the small number of cases and the lack of profit potential, pharmaceutical companies have not invested much in the development of possible treatments. However, over the last few years, new therapies for rare diseases have emerged, giving physicians a chance to offer personalized treatment. With this paper, we aim to present some of the orphan neurological diseases for which new drugs have been developed lately. We have conducted a literature review of the papers concerning rare diseases and their treatment, and we have analyzed the existing studies for each orphan drug. For this purpose, we have used the Google Scholar search engine and the Orphanet. We have selected the studies published in the last 15 years. Since the formation of the National Organization for Rare Diseases, the Orphan Drug Act, and the National Institutes of Health Office of Rare Diseases, pharmacological companies have made a lot of progress concerning the development of new drugs. Therefore, diseases that until recently were without therapeutic solutions benefit today from personalized treatment. We have detailed in our study over 15 neurological and systemic diseases with neurological implications, for which the last 10-15 years have brought important innovations regarding their treatment. Many steps have been taken towards the treatment of these patients, and the humanity and professionalism of the pharmaceutical companies, along with the constant support of the patient's associations for rare diseases, have led to the discovery of new treatments and useful future findings.

Diversity-Oriented Biosynthesis Yields l-Kynurenine Derivative-Based Neurological Drug Candidate Collection

Natural product libraries with a remarkable range of biological activities play pivotal roles in drug discoveries due to their extraordinary structural complexity and immense diversity. l-Kynurenine (l-Kyn)-based derivatives are privileged pharmacophores that exhibit diverse therapeutic implications in neurological disorders. However, the difficulty in obtaining l-Kyn analogues with different skeletal structures has recently led to a decline in its medicinal research. Herein, we report a two-step, one-pot protocol for diversity-oriented biosynthesis of a collection of previously intractable l-Kyn-like compounds. The success of these challenging transformations mainly depends on unlocking the new catalytic scope of tryptophan 2,3-dioxygenases, followed by rational site-directed mutagenesis to modify the substrate domains further. As a result, 18 kynurenine analogues with diverse molecular scaffolds can be rapidly assembled in a predictable manner with 20-83% isolated yields, which not only fill the voids of the catalytic profile of tryptophan 2,3-dioxygenases with an array of substituent groups (e.g., F, Cl, Br, I, CH3, OCH3, and NO2) but also update the current understanding of its substrate spectrum. Our work highlights the great potential of existing enzymes in addressing long-standing synthetic challenges for facilitating the development or discovery of new drug candidates. Furthermore, our approach enables translating the reaction parameters from Eppendorf tubes to 1 L scale, affording l-4-Cl-Kyn and l-5-Cl-Kyn both on a gram scale with more than 80% isolated yields, and provides a promising alternative to further industrial applications.

In vivo monitoring of brain pharmacokinetics and pharmacodynamics with cerebral open flow microperfusion.

In vivo investigation of brain pharmacokinetics and pharmacodynamics (PK/PD) is an integral part of neurological drug development. However, drugs intended to act in the brain may reach it at very low concentrations due to the protective effect of the blood-brain barrier (BBB). Consequently, very sensitive measurement methods are required to investigate PK/PD of drugs in the brain. Also, these methods must be capable of continuously assessing cerebral drug concentrations with verifiable intact BBB, as disrupted BBB may lead to compound efflux from blood into brain and to biased results. To date, only a few techniques are available that can sensitively measure drug concentrations in the brain over time; one of which is cerebral open flow microperfusion (cOFM). cOFM's key features are that it enables measurement of cerebral compound concentrations with intact BBB, induces only minor tissue reactions, and that no scar formation occurs around the probe. The membrane-free cOFM probes collect diluted cerebral interstitial fluid (ISF) samples that are containing the whole molecule spectrum of the ISF. Further, combining cOFM with an in vivo calibration protocol (e.g. Zero Flow Rate) enables absolute quantification of compounds in cerebral ISF. In general, three critical aspects have to be considered when measuring cerebral drug concentrations and recording PK/PD profiles with cOFM: (a) the BBB integrity during sampling, (b) the status of the brain tissue next to the cOFM probe during sampling, and (c) the strategy to absolutely quantify drugs in cerebral ISF. This work aims to review recent applications of cOFM for PK/PD assessment with a special focus on these critical aspects.

Experimental Models of In Vitro Blood-Brain Barrier for CNS Drug Delivery: An Evolutionary Perspective.

Central nervous system (CNS) disorders represent one of the leading causes of global health burden. Nonetheless, new therapies approved against these disorders are among the lowest compared to their counterparts. The absence of reliable and efficient in vitro blood-brain barrier (BBB) models resembling in vivo barrier properties stands out as a significant roadblock in developing successful therapy for CNS disorders. Therefore, advancement in the creation of robust and sensitive in vitro BBB models for drug screening might allow us to expedite neurological drug development. This review discusses the major in vitro BBB models developed as of now for exploring the barrier properties of the cerebral vasculature. Our main focus is describing existing in vitro models, including the 2D transwell models covering both single-layer and co-culture models, 3D organoid models, and microfluidic models with their construction, permeability measurement, applications, and limitations. Although microfluidic models are better at recapitulating the in vivo properties of BBB than other models, significant gaps still exist for their use in predicting the performance of neurotherapeutics. However, this comprehensive account of in vitro BBB models can be useful for researchers to create improved models in the future.

Computer-Aided Drug Design towards New Psychotropic and Neurological Drugs.

Central nervous system (CNS) disorders are a therapeutic area in drug discovery where demand for new treatments greatly exceeds approved treatment options. This is complicated by the high failure rate in late-stage clinical trials, resulting in exorbitant costs associated with bringing new CNS drugs to market. Computer-aided drug design (CADD) techniques minimise the time and cost burdens associated with drug research and development by ensuring an advantageous starting point for pre-clinical and clinical assessments. The key elements of CADD are divided into ligand-based and structure-based methods. Ligand-based methods encompass techniques including pharmacophore modelling and quantitative structure activity relationships (QSARs), which use the relationship between biological activity and chemical structure to ascertain suitable lead molecules. In contrast, structure-based methods use information about the binding site architecture from an established protein structure to select suitable molecules for further investigation. In recent years, deep learning techniques have been applied in drug design and present an exciting addition to CADD workflows. Despite the difficulties associated with CNS drug discovery, advances towards new pharmaceutical treatments continue to be made, and CADD has supported these findings. This review explores various CADD techniques and discusses applications in CNS drug discovery from 2018 to November 2022.

The effect of skin traction on pain relief in patients with isolated intertrochanteric fractures, a randomized clinical trial

BackgroundHip fractures are common in elderly patients. The surgery is usually delayed due to underlying conditions, and pain control is crucial while the patient is cleared for surgery. In this randomized controlled trial (RCT) study, we hypothesized that the application of skin traction in patients with intertrochanteric fracture does not significantly change the Visual Analogue Score (VAS) of pain.MethodsThis is a prospective, single institution, parallel randomized controlled trial. Two hundred and twenty-nine patients with isolated intertrochanteric fractures were enrolled in the study. Patients with neurologic issues, drug addiction, scars or swelling, or vascular issues at the site of skin traction application were excluded from the study. Patients were divided into two groups: group A included 97 patients, and group B included 95 patients. Skin traction was applied for group A, while only a soft pillow was put beneath the patients’ knees in the other group. The VAS score was measured after the diagnosis, two hours before the operation, and 24 h after the surgery. The morphine dosage administered per day was documented for both groups.ResultsAfter excluding patients with postoperative delirium, 154 patients (55 males and 99 females) with isolated intertrochanteric fractures (69 right-sided and 85 left-sided), and a mean age of 70 ± 10 remained in the study. There were no significant differences between the two groups regarding age, gender, and mean time from injury to admission (P > .05). The mean VAS score measures and morphine dosage administered per day were not significantly different between the two groups (P > .05). Both groups experienced significant pain relief 24 h postoperatively (P < .001).ConclusionPre-operative skin traction application affected neither the patients' VAS scores nor the mean morphine dosage per day in patients with isolated intertrochanteric fractures. Our data does not support the routine application of pre-operative skin traction in patients with intertrochanteric fractures.Trial registrationThe project was registered in the Iranian Registry of Clinical Trials (registration reference: IRCT20180729040636N3, registration date: 01/07/2020).Level of evidence1.

A potassium-chloride co-transporter promotes tumor progression and castration resistance of prostate cancer through m6A reader YTHDC1

SLC12A5, a neuron-specific potassium-chloride co-transporter, has been reported to promote tumor progression, however, the underlying mechanism remains unclear. Here we report that SLC12A5 functions as an oncogene to promote tumor progression and castration resistance of prostate cancer through the N6-methyladenosine (m6A) reader YTHDC1 and the transcription factor HOXB13. We have shown that the level of SLC12A5 was increased in prostate cancer, in comparison to its normal counterparts, and further elevated in castration-resistant prostate cancer (CRPC). The enhanced expression of SLC12A5 mRNA was associated with neuroendocrine prostate cancer (NEPC) progression and poor survival in prostate cancer. Furthermore, we demonstrated that SLC12A5 promoted the castration resistance development of prostate cancer in addition to the cell proliferation and migration. Interestingly, SLC12A5 was detected in the cell nucleus and formed a complex with nuclear m6A reader YTHDC1, which in turn upregulated HOXB13 to promote the prostate cancer progression. Therefore, our findings reveal a mechanism that how the potassium-chloride cotransporter SLC12A5 promotes the tumor progression and provide a therapeutic opportunity for prostate cancer to apply the neurological disorder drug SLC12A5 inhibitors.

Unraveling the Interaction of a Neurological Drug Rivastigmine with Human Insulin Protein: A Biophysical Method in Combination with Molecular Docking and Molecular Dynamics Simulation

The study aims to examine the aggregation of proteins due to their association with various conformational problems including well-known neurodegenerative diseases like Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease. In this context, we have studied the mechanistic route of the neurological drug rivastigmine on human insulin (HI) protein aggregation. The Thioflavin T and light scattering studies establish that the drug has the ability to inhibit HI fibrillation. It is pertinent to note here that rivastigmine has been anticipated to cross the blood–brain barrier. The dye 8-anilino-1-naphthalenesulfonic acid binding assays exhibit that the drug interferes with the hydrophobic domain of the protein because of intermolecular interaction. Furthermore, molecular docking and molecular dynamics simulation studies revealed the interactions of rivastigmine at the receptor site of acetylcholinesterase (AChE) and Aβ-42, thereby inhibiting the hydrolytic activity. Rivastigmine forms a hydrogen bond with the Tyr337 residue of AChE and His14 (chain C) and Gly33 (chain A) residues of Aβ-42, in addition to several weak interactions. The results showed the fundamental mechanisms of the inhibition of HI fibrillation by neurological drugs, which may provide ideas about the rational design of new lead therapeutics against amyloidosis.

Safety and Tolerability of Lumbar Catheterization and Lumbar Puncture for Cerebrospinal Fluid Analysis in Clinical Neurology Drug Studies

Safety and Tolerability of Lumbar Catheterization and Lumbar Puncture for Cerebrospinal Fluid Analysis in Clinical Neurology Drug Studies

Rapid One-Pot Microwave Assisted Green Synthesis Nitrogen Doped Carbon Quantum Dots as Fluorescent Precursor for Estimation of Modafinil as Post-Covid Neurological Drug in Human Plasma with Greenness Assessments

The neuro-stimulant anti-narcoleptic drug as modafinil (MOD) is used to treatment neurological conditions caused by COVID-19. MOD was used to treatment narcolepsy, shift-work sleep disorder, and obstructive sleep apnea-related sleepiness. So, an innovative, quick, economical, selective, and ecologically friendly procedure was carried out. A highly sensitive N@CQDs technique was created from green Eruca sativa leaves in about 4 min using microwave synthesis at 700 w. The quantum yield of the synthesized N@CQDs was found to be 41.39%. By increasing the concentration of MOD, the quantum dots' fluorescence intensity was gradually quenched. After being excited at 445 nm, the fluorescence reading was recorded at 515 nm. The linear range was found to be in the range 50 – 700 ng mL−1 with lower limit of quantitation (LOQ) equal to 45.00 ng mL−1. The current method was fully validated and bio analytically according to (US-FDA and ICH) guidelines. Full characterization of the N@CQDs has been conducted by high resolution transmission electron microscope (HRTEM), Zeta potential measurement, fluorescence, UV–VIS, and FTIR spectroscopy. Various experimental variables including pH, QDs concentration and the reaction time were optimized. The proposed study is simply implemented for the therapeutic drug monitoring system (TDMS) and various clinical laboratories for further pharmacokinetic research.

Drug-induced fall risk in older patients: A pharmacovigilance study of FDA adverse event reporting system database.

Objectives: As fall events and injuries have become a growing public health problem in older patients and the causes of falls are complex, there is an emerging need to identify the risk of drug-induced falls. Methods: To mine and analyze the risk signals of drug-induced falls in older patients to provide evidence for drug safety. The FDA Adverse Event Reporting System was used to collect drug-induced fall events among older patients. Disproportionality analyses of odds ratio (ROR) and proportional reported ratio were performed to detect the adverse effects signal. Results: A total of 208,849 reports (34,840 fall events and 1,898 drugs) were considered. The average age of the included patients was 76.95 ± 7.60years, and there were more females (64.47%) than males. A total of 258 drugs with positive signals were detected to be associated with drug-induced fall incidence in older patients. The neurological drugs (104, 44.1%) with the largest number of positive detected signals mainly included antipsychotics, antidepressants, antiparkinsonian drugs, central nervous system drugs, anticonvulsants and hypnotic sedatives. Other systems mainly included the circulatory system (25, 10.6%), digestive system (15, 6.4%), and motor system (12, 5.1%). Conclusion: Many drugs were associated with a high risk of falls in older patients. The drug is one of the critical and preventable factors for fall control, and the risk level of drug-induced falls should be considered to optimize drug therapy in clinical practice.

3D printed neural tissues with in situ optical dopamine sensors

Engineered neural tissues serve as models for studying neurological conditions and drug screening. Besides observing the cellular physiological properties, in situ monitoring of neurochemical concentrations with cellular spatial resolution in such neural tissues can provide additional valuable insights in models of disease and drug efficacy. In this work, we demonstrate the first three-dimensional (3D) tissue cultures with embedded optical dopamine (DA) sensors. We developed an alginate/Pluronic F127 based bio-ink for human dopaminergic brain tissue printing with tetrapodal-shaped-ZnO microparticles (t-ZnO) additive as the DA sensor. DA quenches the autofluorescence of t-ZnO in physiological environments, and the reduction of the fluorescence intensity serves as an indicator of the DA concentration. The neurons that were 3D printed with the t-ZnO showed good viability, and extensive 3D neural networks were formed within one week after printing. The t-ZnO could sense DA in the 3D printed neural network with a detection limit of 0.137 μM. The results are a first step toward integrating tissue engineering with intensiometric biosensing for advanced artificial tissue/organ monitoring.

Participant Recruitment From Low- and Middle-Income Countries for Pivotal Trials of Drugs Approved by the U.S. Food and Drug Administration : A Cross-Sectional Analysis.

Many participants in clinical trials supporting U.S. Food and Drug Administration (FDA) drug approvals are recruited from outside the United States, including from low- and middle-income countries (LMICs). Where participants are recruited for pivotal trials has implications for ethical research conduct and generalizability. To describe LMIC recruitment for pivotal trials of newly approved drugs for cancer, neurologic disease, and cardiovascular disease. Cross-sectional analysis. Pivotal trials of new cancer, cardiovascular, and neurologic drugs approved from 2012 to 2019 matched to ClinicalTrials.gov, FDA records, and publications. Host countries and available per country enrollments were extracted. The primary end point was the proportion of pivotal trials enrolling participants in LMICs. The secondary end point was the proportion of pivotal trial participants contributed by LMICs for each indication area. Data were obtained from 66 new drugs and 144 pivotal clinical trials. All cardiovascular approvals (12 drugs, 29 trials) and neurologic approvals (26 drugs, 54 trials) were analyzed, as well as a random sample of cancer approvals (28 of 85 drugs [33%]) matched to their pivotal trials (61 of 210 trials [29%]). Among the trials, 56% in cancer, 79% in cardiovascular disease, and 56% in neurology recruited from an LMIC. For multicountry trials, country-level enrollment figures were not available for 71 trials (55%). For those reporting per country enrollment, the percentage of participants recruited from LMICs was 8% for cancer trials, 36% for cardiovascular trials, and 17% for neurology trials. The study was limited to FDA-approved drugs in 3 areas, including a sample of cancer drugs. Pivotal trials of nonapproved drugs or drugs for other indications were not captured. Most pivotal trials for FDA-approved drugs recruit from LMICs. Publications and FDA documents generally do not provide country-level data on recruitment. None.