Pathological neovascularization is the leading cause of childhood blindness in retinopathy of prematurity (ROP). Anti-vascular endothelial growth factor agents are commonly used to treat this condition, yet their variable efficacy and off-target effects demand alternative strategies. Here, we investigated the relationship between retinal dopamine (DA) dynamics and pathological angiogenesis in the oxygen-induced retinopathy (OIR) mouse model mimicking ROP pathogenesis. We determined the individual effects of apomorphine (APO), a non-selective DA receptor agonist, and selective agonists or antagonists of dopamine D1 receptor (Drd1) and dopamine D2 receptor (Drd2), on pathological neovascularization. Integrating single-cell RNA sequencing with Müller cell-specific Drd2 knockout OIR mice, we identified that Drd2-mediated signaling in Müller cells orchestrates hypoxia-inducible factor alpha and vascular endothelial growth factor A biosynthesis in Müller cells during the hypoxic-ischemic phase of OIR. Collectively, OIR-induced dopaminergic deficiency and impaired Drd2 activity in Müller cells synergistically exacerbate pathological angiogenesis. © 2026 The Pathological Society of Great Britain and Ireland.

Introduction Apomorphine (APO) is inherently unstable in aqueous solutions, as it forms auto-oxidation products. The study investigates the degradation kinetics of APO as the function of pH and evaluates the stabilizing effects of antioxidants (i.e. ascorbic acid (AA) and sodium metabisulfite (SMB)) on APO solution formulations. Significance To understand combined impact of pH-adjustment, buffer concentrations and antioxidant addition on the degradation kinetics of APO. Methods The degradation kinetics of APO in solutions and the antioxidant effect were investigated with a reversed-phase HPLC system. The influences of pH value on degradation of APO were studied in aqueous solutions. Stability studies were performed under a nitrogen blanket and protected from light to minimize oxidative and light-induced degradation and allow aqueous degradation in order to establish the pH-rate profile of APO in aqueous media. Results APO in aqueous solution showed rapid degradation with pseudo-first-order kinetics at 25 °C. The log ko -pH profile indicated that the optimal stability range for APO was at acidic pH values of 2.4–2.6. Degradation rate constants were determined for reactions run over pH values range of 2.0–8.0. The lowest molar buffer concentration used at 0.01 M, resulted in a more stable APO formulation. AA used at 1% as an antioxidant in APO formulation appeared to be superior against APO degradation with 97.4% of APO remaining, while 50% SMB formulation had the most APO degradation with 94.25% APO remaining after 6 months. Conclusion The APO aqueous formulation at pH 2.4–2.6 with 1% AA is recommended to maximize stability and clinical tolerability.

Diabetic-induced erectile dysfunction (DIED) is a frequent complication of diabetes mellitus. Qianlie Beixi Capsules, a formulation of traditional Chinese medicine, have long been used for its management. The effectiveness of Qianlie Beixi Capsules in treating DIED was evaluated together with an exploration of their possible mechanism of action. Streptozotocin (STZ) was administered to rats to induce diabetes, with confirmation of erectile dysfunction using apomorphine (APO). The animals were allocated to six groups: the blank control (NC), model (M), Qianlie Beixi Capsules low-dose (QD), Qianlie Beixi Capsules medium-dose (QZ), Qianlie Beixi Capsules high-dose (QG), and HIF-1α inhibitor (YC) groups. After 2 weeks of treatment, serum levels of testosterone (T), Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), and Endothelial Microparticles (EMPs) were measured. Penile histology was analyzed for structural alterations. Furthermore, Western blotting and reverse transcription quantitative polymerase chain reaction (RT-qPCR) were utilized to assess levels of mammalian target of rapamycin(mTOR), p70 ribosomal protein S6 kinase(p70s6k), hypoxia-inducible factor 1-alpha(HIF-1α), vascular endothelial growth factor(VEGF), and endothelial nitric oxide synthase(eNOS ) in the corpus cavernosum. The QZ and QG groups demonstrated markedly increased penile erection frequency relative to the model rats (p < .05). Histological analyses revealed increased smooth muscle cell densities, reduced collagen deposition, and a decrease in erythrocytes within the blood sinuses in these groups. Expression of HIF-1α and VEGF proteins was significantly reduced (p < .05), while eNOS expression was elevated (p < .05). Moreover, serum levels of LOX-1 and EMPs were markedly reduced (p < .05) in the QZ and QG groups. Qianlie Beixi Capsules improve DIED by modifying the mTOR/HIF-1α/VEGF signaling axis, which additionally increases penile endothelial function and reduces endothelial fibrosis.

This research aimed to examine the impact of co-transplantation of ethyl stearate (PubChem CID: 8122) and neural stem cells (NSCs) on endogenous NSCs in Parkinson's disease (PD) model rats, and also determine the impact of ethyl stearate on quiescent neural stem cells (qNSCs) and explore its possible mechanism. The induction of PD rats was achieved through the injection of 6-hydroxydopamine (6-OHDA) into the right striatum (STR) and substantia nigra (SN). Transplant treatment was then followed for 6 weeks in the right STR. Apomorphine (APO)-induced rotation behavior and the pole climbing test were used to assess the effects of transplant treatment in each group. Western blotting (WB) and immunofluorescence staining were used to observe changes in endogenous NSCs. The effect of ethyl stearate on qNSCs was examined invitro, with detection of associated indicators achieved through WB, immunofluorescence, flow cytometry and qRT-PCR. Co-transplantation of NSCs with ethyl stearate significantly ameliorated motor deficits in PD rats and upregulated the expression of tyrosine hydroxylase (TH), Sox2, and Nestin. We established an invitro system for NSC quiescence and activation. In qNSCs, ethyl stearate treatment increased Ki67 positivity and reduced the proportion of cells in the G0-G1 phase of the cell cycle, whereas withdrawal of ethyl stearate exerted the opposite effects. Ethyl stearate also downregulated EphB2 protein levels and upregulated p-AKT and CyclinD1 in qNSCs; these effects were reversed upon its removal. These findings imply that co-transplantation of NSCs and ethyl stearate may help ameliorate motor impairment in PD rats by activating endogenous NSCs and promoting their development into dopaminergic neurons. Ethyl stearate may regulate the entry and exit of NSCs from quiescence through the EphB2/AKT/CyclinD1 pathway.

Dextrin-based nanosponges (D-NS) are promising candidates for oral drug delivery due to their biocompatibility, mucoadhesive properties, and tunable swelling behavior. In this study, pH-sensitive nanosponges were synthesized using β-cyclodextrin (β-CD), GluciDex®2 (GLU2), and KLEPTOSE® Linecaps (LC) as building blocks, crosslinked with pyromellitic dianhydride (PMDA) and citric acid (CA). The nanosponges were mechanically size-reduced via homogenization and ball milling, and characterized by FTIR, TGA, dynamic light scattering (DLS), and zeta potential measurements. Swelling kinetics, cross-linking density (determined using Flory-Rehner theory), rheological behavior, and mucoadhesion were evaluated under simulated gastric and intestinal conditions. The β-CD:PMDA 1:4 NS was selected for drug studies due to its optimal balance of structural stability, swelling capacity (~863% at pH 6.8), and highest apomorphine (APO) loading (8.23%) with 90.58% encapsulation efficiency. All nanosuspensions showed favorable polydispersity index values (0.11-0.30), homogeneous size distribution, and stable zeta potentials, confirming suspension stability. Storage at 4 °C for six months revealed no changes in physicochemical properties or apomorphine (APO) degradation, indicating protection by the nanosponge matrix. D-NS exhibited tunable swelling, pH-responsive behavior, and mucoadhesive properties, with nanoparticle-mucin interactions quantified by the rheological synergism parameter (∆G' = 53.45, ∆G″ = -36.26 at pH 6.8). In vitro release studies demonstrated slow, sustained release of APO from D-NS in simulated intestinal fluid compared to free drug diffusion, highlighting the potential of D-NS as pH-responsive, mucoadhesive carriers with controlled drug release and defined nanoparticle-mucin interactions.

Stereotactic infusion of rotenone into the SN induced a late-stage model of Parkinson's disease.

Abstract Apomorphine, a potent dopamine agonist, plays a significant role in the management of advanced Parkinson's disease, and requires careful monitoring of the drug and its impurities for safety and efficacy. The USP monograph for Apomorphine Hydrochloride currently uses classical methods—titrimetry for assay and Thin-Layer Chromatography (TLC) for impurity testing—which, although effective, are not comparable in accuracy and speed to newer chromatographic techniques like High-Performance Liquid Chromatography (HPLC). For this, an HPLC method was developed using a C18 column, which possesses hydrophobic interaction capacity, and an isocratic elution mode with a mobile phase of 10 mM phosphate buffer (pH 3.0) and methanol (87.5:12.5) containing 0.075% L-tartaric acid. This combination allowed efficient separation of apomorphine from impurities without compromising stability.The method was thoroughly validated according to International Council for Harmonisation (ICH) guidelines and exhibited very good specificity, precision, accuracy, linearity, and robustness. The validation results demonstrated a good linear correlation (r = 0.999) between the peak area and the apomorphine concentration, excellent precision (repeatability of 0.23% and intermediate precision of 0.56%), and accuracy (recoveries of 99.72–100.08%). Robustness was confirmed by minimal variation in percentage recovery (R = 1.3%), and specificity was confirmed by the absence of interfering peaks caused by excipients or formulation components. The method has been successfully employed in the analysis of apomorphine and impurities in commercial products, proving itself reliable from batch to batch. This HPLC method represents a significant improvement over conventional methods, as it provides a precise and quicker approach for the quality control of apomorphine medicinal products.

Necroptosis, a form of programmed cell death, has emerged as a promising therapeutic target. Although several RIPK1 inhibitors have demonstrated favorable safety profiles in clinical trials, clinical translation of necroptosis-targeted therapies remains limited by modest efficacy, limited specificity, and species-specific activity of compounds such as necrosulfonamide (NSA). To resolve these challenges, this study identified a potential necroptosis inhibitor from a clinical drug library. Apomorphine (APO), a non-addictive morphine derivative used to treat Parkinson’s disease, was found to inhibit necroptosis by sterically blocking key residues involved in mixed lineage kinase domain-like protein (MLKL) activation and oligomerization, as confirmed by nuclear magnetic resonance analysis. APO is redox sensitive and prone to auto-oxidation. The oxidized form of APO (Ox-APO) showed stronger binding to MLKL than the reduced form of APO (Re-APO), as demonstrated by surface plasmon resonance analysis. Ox-APO significantly ameliorated tissue damage in two murine necroptosis models: dextran sulfate sodium (DSS)-induced colitis and acetaminophen (APAP)-induced liver injury. Collectively, these data highlight the therapeutic potential of APO as a necroptosis-specific inhibitor in necroptosis-related diseases in both humans and mice.

Background: Parkinson's disease (PD) is one of the most prevalent neurodegenerative disorders, characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNc). Among the available treatments, levodopa (L-Dopa) and apomorphine (APO) remain the most effective symptomatic treatments for managing PD. Objectives: This study aimed not only to compare the effects of L-Dopa and APO on the behavioral and histopathological characteristics of a rotenone-induced PD animal model but also to evaluate the levels of alpha-synuclein and tyrosine hydroxylase (TH) in the model after treatment. Methods: The PD was induced via stereotaxic injection of rotenone into Wistar rats. After four weeks, the animals underwent treatment with either L-Dopa or APO for an additional four weeks. Behavioral assessments were conducted, along with immunostaining to evaluate alpha-synuclein and TH levels. Beta-amyloid accumulation was assessed using Congo red (CR) staining in ipsilateral and contralateral SNc regions. Results: The Morpurgo, stride width, and left stride length findings showed no significant differences among the groups. No significant difference was observed between the treated groups (L-Dopa and APO) and the control group regarding the right stride length from the first to fourth week post-treatment. Immunohistochemical (IHC) staining revealed that L-Dopa and APO administration did not alter the over-expressed alpha-synuclein levels or the decreased TH levels induced by rotenone within the SNc region in the rat model. Reduced amyloid deposition was observed in the ipsilateral region of the L-DOPA-treated group, as well as in the contralateral SNc of both the L-DOPA and APO-treated groups. Conclusions: The L-DOPA and APO, though effective for symptomatic PD treatment in humans, showed only partial behavioral improvement and modest reduction in the rotenone-induced PD rat model. The differences in drug effects among humans and various animal models arise from a complex interplay of biological, physiological, and methodological factors.

Conventional delivery of apomorphine hydrochloride (APO) for management of 'OFF' periods in Parkinson's disease is limited to subcutaneous or sublingual delivery, and would substantially benefit from a transdermal drug delivery system (TDDS). Minimal progression has been made thus far in this area, with current literature presenting debatably flawed or inconsistent experimental design for ex vivo percutaneous permeation and deposition studies, a crucial step in understanding TDDS performance. Provided here is an improved, robust, versatile and easily-transferred analytical methodology, fully validated in accordance with guidelines provided by the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH). Reversed-phase high performance liquid chromatography (RP-HPLC) is employed with ultraviolet-visible (UV) light or fluorescence intensity (FID) detection in conjunction with a Franz diffusion-cell setup that ensures stability of APO and uses physiologically relevant neonatal porcine skin. Thus, this methodology may be reliably employed by future researchers developing an APO TDDS. To demonstrate application, a superficial investigation into model pressure-sensitive adhesive (PSA) patch systems provided sustained percutaneous delivery of up to 4.015 ± 2.361µg/cm2/hr APO over a 24-hour period. These offer brief insight into a system that has yet to be studied in-depth for percutaneous delivery of APO, and highlight the importance of alternative penetration enhancers or enhancement techniques in developing a TDDS with clinical potential.

Effect of imipramine on ejaculatory dysfunction in a rat hypogastric nerve injury model.

Initiation of apomorphine hydrochloride injection (Apokyn) in the absence of an antiemetic in people with Parkinson disease

Apomorphine (APO), a dopamine agonist, activates nuclear factor erythroid 2-related factor 2 (Nrf2) and exerts antioxidant effects, making it a promising candidate for neuroprotection against oxidative stress. This study evaluated neuroplasticity-enhancing properties of newly synthesized APO derivatives, focusing on their ability to promote neurite outgrowth in PC12 cells under nerve growth factor (NGF) stimulation. D55, an APO derivative, retains the hydroxyl group at APO's 11th position while substituting the 10th with an ethoxy group. D55 exhibited the highest potency (EC50 = 0.5661 nM), significantly enhancing neurite outgrowth. APO demonstrated the highest efficacy (Emax ~10-fold increase), while edaravone (Eda) required higher concentrations (EC50 = 22.5 nM) for moderate effects (Emax ~4-fold increase). D30, in which the 11th hydroxyl was replaced with a methoxy group, had no effect. Neurite outgrowth-promoting effects of APO, D55, and Eda were significantly attenuated by Nrf2 siRNA knockdown, confirming that their neuroplasticity effects are Nrf2-mediated. These findings confirm that D55 is a highly potent Nrf2-activating compound with strong neuroprotective potential, providing new insights into its therapeutic applications for neurodegenerative diseases associated with oxidative stress.

To compare the efficacy of ropinirole (ROP) eye drops and IV apomorphine (APO) for inducing emesis in dogs in an emergency setting and to compare the adverse effects of these two drugs. Prospective, randomized, clinical trial between October 2021 and March 2023. Two private specialty referral centers. One hundred thirty-two client-owned dogs with known or suspected foreign material ingestion. Dogs were randomly assigned to receive ROP (n=63) or APO (n=69) to induce emesis. If emesis did not occur within 20min, subjects were re-dosed with the same medication and dosage. The reason for emesis, success, time to first emesis, number of emetic events, and need for rescue antiemetic were evaluated. Heart rate, respiratory rate, and temperature were tracked at time 0 and at 20 and 40min. Adverse events were categorized into major events (e.g., tachycardia, hyperthermia, tachypnea), minor events (e.g., sedation, ocular irritation), and protracted vomiting (vomiting past 30min). ROP's first-dose success was 81% (51/63) compared with APO's 99% success (68/69) (p<0.001). The median time to the first emetic event was 8.6min in the ROP group and 1.6min in the APO group (P<0.001). Antiemetic rescue was required in 37% (23/63) of dogs receiving ROP and 0% (0/69) of dogs receiving APO (P<0.001). The major adverse event frequency between groups was not different (P=0.604); however, the minor adverse event frequency was statistically significant (P=0.011). ROP had a lower first-dose emetic success rate, a longer median time to the first emetic event, an increased occurrence of minor adverse events, and a higher frequency of protracted vomiting necessitating rescue therapy. These findings suggest APO is a clinically superior emetic agent for dogs presenting to the emergency department requiring rapid decontamination.

In Poland, not all forms of device-aided therapies for advanced Parkinson's Disease (APD) are currently available. We aimed to produce a consensus recommendation from Polish movement disorders experts after discussing gaps in the APD care pathway in Poland. Rescue therapy with apomorphine (APO) PEN injection and levodopa-entacapone-carbidopa intestinal gel infusion are not included in Poland's Specialist Therapeutic Programme, and are thus not reimbursed. For APO infusion, only the medication is reimbursed but not the device. Consensus expert opinion is that APD patients in Poland would benefit from additional reimbursement access to these treatment options to improve APD patient care.

In experimental and clinical studies of pharmacological treatments for Alzheimer's disease (AD), the electroencephalogram (EEG) frequency spectrum approach has demonstrated its efficacy in determining the characteristics of pathological changes in the functioning of different cerebral structures, interconnections between them, and disturbances in the brain neurotransmitter systems. The main results have been obtained in frames of traditionally used so-called "classical" EEG frequency bands: delta, theta, alpha, and beta. This unified approach simplifies comparing data from different studies but loses the dynamic peculiarities of the effects because of their time-dependent transition through the borders of the "classical" bands. In this study on non-narcotized freely moving 5xFAD transgenic mice, a model of AD, chronically pretreated with a non-selective dopamine (DA) receptor agonist, apomorphine (APO), we analyze the transitory EEG effects of acute APO injection in different brain areas by use of our "time-frequency" clustering program. The acute injection of APO was used to compare DA receptor sensitivity in 5xFAD mice pretreated with either APO or saline vs. wild-type (WT) mice pretreated with saline. After acute APO injection, the clusters of enhanced EEG activity centered in the theta-alpha frequency range observed in WT mice disappeared in 5xFAD mice pretreated with saline and practically recovered in 5xFAD mice pretreated with APO. In 5xFAD mice pretreated with saline, the sensitivity of DA receptors was disturbed; chronic APO pretreatment mainly recovered this characteristic in 5xFAD mice. The "clustering" of pharmacological EEG effects and their time-dependent transition between classical frequency bands is a new effective approach for analyzing cerebral neurotransmission in neurodegenerative pathologies.

The rising occurrence of erectile dysfunction related to diabetes mellitus (DMED) has led to the creation of new medications. Proanthocyanidins (PROs) is a potential agent for DMED. In this study, the DMED rat model was established using streptozotocin (STZ) and erectile function was assessed using apomorphine (APO) in rats. Following this, the rats were subjected to oral treatment with PRO. Then, we evaluated the influence of PROs on DMED rats. The findings suggest that PROs significantly enhance erectile function in DMED rats. PROs modulated glucose and lipid metabolism in DMED rats by decreasing blood glucose and lipid levels while increasing liver glycogen and serum insulin levels. Furthermore, PROs enhanced vascular endothelial function in DMED rats by augmenting nitric oxide (NO) levels and reducing the levels of endothelin-1 (ET-1) and lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1). Additionally, PROs have been shown to elevate testosterone (T) levels, mitigate pathological testicular damage, and enhance sperm concentration and survival rates. Finally, the core targets were screened using network pharmacology, followed by validation through molecular docking, enzyme-linked immunoassay (ELISA), and real-time PCR methodologies. Our findings imply that PROs may treat DMED by elevating AKT1 levels while concurrently diminishing CASP3 levels, thereby effectively regulating the PI3K-Akt signaling pathway. Overall, these results support using PROs as a potential candidate for the treatment of DMED.

Growing evidence indicates that activation of cannabinoid type 2 (CB2) receptors protects dopamine neurons in the pathogenesis of Parkinson's disease (PD). However, the mechanisms underlying neuroprotection mediated by CB2 receptors are still elusive. In this study, we investigated the effects of CB2 receptor activation on 6-hydroxydopamine (6-OHDA)-induced dopamine neuron degeneration and iron accumulation in the substantia nigra (SN) of rats. We found that treatment with JWH133, a selective CB2 receptor agonist, significantly improved the apomorphine (APO)-induced rotational behavior in 6-OHDA-treated rats. The decreased numbers of tyrosine hydroxylase (TH)-positive neurons and reduced TH protein expression in the lesioned SN of rats were effectively restored by JWH133. Moreover, we found that JWH133 inhibited the increase of iron-staining cells in the lesioned SN of rats. To explore the protective mechanisms of activation of CB2 receptors on dopamine neurons, we further observed the effect of JWH133 on 1-methyl-4-phenylpyridinium (MPP+)-treated primary cultured ventral mesencephalon (VM) neurons from rats. We found that JWH133 significantly inhibited the increase of intracellular reactive oxygen species (ROS), the activation of Caspase-3, the decrease of mitochondrial transmembrane potential (ΔΨm), and the decrease of Bcl-2/Bax protein expression caused by MPP+ treatment. JWH133 also inhibited the MPP+-induced upregulation of divalent metal transporter-1 (DMT1) and downregulation of ferroportin 1 (FPN1). Furthermore, JWH133 also suppressed the MPP+-accelerated iron influx in the VM neurons. These results suggest that activation of CB2 receptor suppresses MPP+-induced cellular iron accumulation and prevents neurodegeneration.NEW & NOTEWORTHY Expression of cannabinoid type 2 receptors (CB2Rs) was discovered on dopamine neurons in recent years. The role of CB2R expressed on dopamine neurons in the pathogenesis of Parkinson's disease (PD) has not been fully elucidated. The content of iron accumulation in the brain is closely related to the progress of PD. We verified the inhibitory effect of CB2R on iron deposition in dopamine neurons through experiments, which provided a new idea for the treatment of PD.

Platelet-rich plasma (PRP) shows promise as a regenerative modality for mild-to-moderate erectile dysfunction (ED). However, its efficacy in treating severe ED remains unknown. Blood samples from 8-week-old male rats were used to prepare PRP through a two-step centrifugation procedure, followed by chitosan activation and freeze thaw cycle. A hyperhomocysteinemia (HHcy)-related ED model was established using a methionine-enriched diet, and an apomorphine (APO) test was conducted during the 4 th week. APO-negative rats were divided into two groups and were injected with PRP or saline every 2 weeks. Erectile function and histological analyses of the corpus cavernosum were performed during the 16 th week. The results revealed that erectile function was significantly impaired in rats with HHcy-related ED compared to that in age-matched rats but was improved by repeated PRP injections. Immunofluorescence staining revealed a reduction in reactive oxygen species and additional benefits on the recovery of structures within the corpus cavernosum in rats that received PRP treatment compared to those in the saline-injected control group. Therefore, PRP could enhance functional and structural recovery in a severe HHcy-related ED model. A notable strength of the present study lies in the use of a repeated intracavernous injection method, mirroring protocols used in human studies, which offers more reliable results for translating the findings to humans.

The primary goal was to compare the efficacy of administration of apomorphine (APO) administered by intranasal (IN), transconjunctival (TC), SC and IV routes with ropinirole eye drops for induction of emesis in dogs with a secondary goal to evaluate the time of emesis as well as difficulty in administration. 125 client-owned dogs. Dogs were randomly enrolled between October 1, 2021, and March 30, 2022, into groups of 25: IV APO, IN APO, TC APO, SC APO, and ropinirole eye drops. The IV, SC, and TC groups were dosed at 0.03 mg/kg, the IN group was dosed at 0.06 mg/kg, and the ropinirole group was dosed according to manufacturer guidelines. Data collected included success rate of emesis within 600 seconds, time to emesis, time to administer, and difficulty score. Results were compared to IV with P values and CIs being adjusted for multiple comparisons. Emesis was successful within 600 seconds using IV APO in 22 of 25 dogs. By comparison, IN APO induced emesis in 18 of 25 dogs (P = .63). Ropinirole (14/25), SC APO (6/25), and TC APO (4/25) were significantly less successful (P = .047, P = < .001, and P < 0.001, respectively). When emesis was successful, it occurred most rapidly with TC APO, followed by IN APO and then ropinirole. It was most difficult to administer IV APO and TC APO. Similar to IV APO, IN APO was a rapid, easy, and effective method of inducing emesis in dogs and should be considered when IV administration is not possible. Ropinirole was easy to administer but successfully induced emesis less reliably within a 10-minute timeframe. APO administered TC using the commercially compounded injectable formulation was ineffective.