Eyes on the Prize: Decoding the Ophthalmic Product Regulations and Intricacies of the U.S. Food and Drug Administration Approval.

The dynamic and continuously evolving field of ophthalmology necessitates rigorous regulatory oversight in the United States. This review outlines the multifaceted Food and Drug Administration's (FDA) approval process for ophthalmic products, detailing the classifications, pathways, and regulatory compliance for devices, drugs, biologics, and combination products. Particular emphasis is placed on distinct frameworks for Class I, II, and III devices, as well as regulations for drugs, biologics, and combination products.

A novel liposomal bupivacaine formulation to produce ultralong-acting analgesia.

Background: Currently available local anesthetics have relatively brief durations of action. An ultralong-acting local anesthetic would benefit patients with acute and chronic pain. The authors prepared and characterized a novel liposomal bupivacaine formulation using remote loading of bupivacaine along an ammonium sulfate gradient and assessed its efficacy in humans.

Analgesic duration and kinetics of liposomal bupivacaine after subcutaneous injection in mice.

1. The objective of the present study was to assess the time-course profile of analgesia and bupivacaine concentrations at the site of injection after subcutaneous administration of a single dose of standard bupivacaine or a novel controlled-release liposomal bupivacaine formulation. 2.

Intrathecal administration of liposomal neostigmine prolongs analgesia in mice.

Background: There is substantial evidence that cholinomimetic drugs increase pain threshold. However, the profound side effects of these agents have limited their clinical use either as analgesics or as analgesic adjuncts. A delivery system that would assure a slow and sustained drug release may be of value in ameliorating the problem of untoward effects.

DRV liposomal bupivacaine: preparation, characterization, and in vivo evaluation in mice.

Purpose: To evaluate the dehydration-rehydration technique to prepare a formulation of liposomal bupivacaine, and to assess its analgesic efficacy.

Methods: Bupivacaine hydrochloride (BUP) was encapsulated into dehydration-rehydration vesicles (DRV) of varying phospholipid (PL) compositions. Two bilayer-forming phospholipids were used, the "fluid" dimyristoyl-phosphatidylcholine and the "solid" distearoyl-phosphatidylcholine (DSPC), with 20 or 40 mol% cholesterol, in the presence of bupivacaine at a 1.

Quantifiable dose-dependent withdrawal after morphine discontinuation in a rat model.

We evaluated the intensity of the withdrawal symptoms after the discontinuation of the morphine infusion in rats. Opiate addiction was induced by progressively increasing intraperitoneal morphine infusion rates. The control group (Group 1) received normal saline.

An in vivo method for the quantitative evaluation of local anesthetics.

We describe a mouse model for evaluation of skin anesthesia after infiltration of local anesthetic. The method involves subcutaneous injection of the anesthetic over the abdomen, and monitoring the vocalization response to electrical stimulus as a measure of analgesia. Prior to drug injection, the vocalization threshold was determined.

Acute ethanol treatment modulates delta opioid receptors in N18TG2 cells.

Background: The in vitro adaptive responses of delta opiate receptors (DOR) to chronic ethanol treatment have been well documented. The acute effects of ethanol on these receptors are not well characterized beyond its effect on ligand binding. The aim of this study was to evaluate the acute effects of clinically relevant concentrations of ethanol (50-200 mm) on the saturation binding kinetics, receptor/ligand internalization, and agonist stimulation of G-protein coupling in N18TG2 cells expressing the Flag epitope-tagged mouse DOR.

Recycling and resensitization of delta opioid receptors.

Exposure to opioids results in the activation of opioid receptors; this is followed by receptor endocytosis. Previously, we showed that delta opioid receptors undergo rapid agonist-mediated internalization and that mutations in the C-tail result in a substantial loss of agonist-mediated internalization. In this study, we investigated the fate of receptors following rapid internalization.

Opioid receptor endocytosis and activation of MAP kinase pathway.

Opioid receptors, members of the G-protein coupled receptor (GPCR) super family, bind to endogenous opioid peptides or opiate drugs and induce a wide variety of signal transduction processes by inhibiting adenylyl cyclase, modulating cation channels, and activating the mitogen-activated protein (MAP) kinases. Similar to other GPCRs, agonist binding causes rapid internalization and down-regulation of opioid receptors. The interdependence between receptor endocytosis and activation of MAP kinase pathway are increasingly being examined.

Effect of intrathecally administered local anesthetics on protein phosphorylation in the spinal cord.

To elucidate the biochemical mechanisms of spinal anesthesia, we studied the effects of procaine and tetracaine on protein phosphorylation in the mouse spinal cord. Mice were injected intrathecally with either procaine, tetracaine (67 mM/approximately 2%, 10 microL, N = 5/drug), or saline (N = 4/group). Five minutes after injection, animals were killed with a guillotine, and the spinal cord was removed.

Spinal anesthesia by local anesthetics stimulates the enzyme protein kinase C and induces the expression of an immediate early oncogene, c-Fos.

To understand the biochemical mechanisms involved in spinal anesthesia, we measured protein kinase C (PKC) activity and expression of immediate early oncogene protein, c-Fos, in the spinal cord. Spinal anesthesia was induced in mice using intrathecal injection of either 10 microL procaine or tetracaine (0.067 M/approximately 2%).

Propofol modulates the effects of chemoconvulsants acting at GABAergic, glycinergic, and glutamate receptor subtypes.

Background: Propofol has been used to treat status epilepticus, but its use in patients with seizure disorders remains controversial, because of concerns that it produces paroxysmal motor phenomenon. Chemoconvulsants act by known discrete mechanisms and neurotransmitters, and therefore, they are useful tools for screening anticonvulsant activity. The main objective of this study was to characterize the effect of propofol pretreatment on convulsions induced by picrotoxin, bicuculline, and strychnine, all which decrease inhibitory neurotransmission, and by N-methyl-D-aspartic acid, kainic acid, and quisqualic acid, which enhance excitatory neurotransmission.

Pertussis and cholera toxins modulate kappa-opioid receptor agonists-induced hypothermia and gut inhibition.

In mice pretreated intracerebroventricularly (i.c.v.

The partition coefficient as a predictor of local anesthetic potency for spinal anesthesia: evaluation of five local anesthetics in a mouse model.

Local anesthetic partition coefficients correlate with drug potencies in vitro, but in vivo data have not always complimented in vitro results. Despite extensive studies on intrathecal anesthetic action, whether there is correlation between the partition coefficient and local anesthetic potency has not been addressed. Mice (n = 150) were randomly allocated into 15 groups.

Regulation of neuropeptide-processing enzymes by nitric oxide in cultured astrocytes.

Nitric oxide (NO), a recently discovered neurotransmitter, has been shown to have a cytostatic effect on cultured glia. A NO-generating agent, S-nitroso-N-acetyl-penicillamine (SNAP), was used to treat C6 glioma and primary cortical astrocytes. The levels of a monobasic peptide-processing enzyme activity and carboxypeptidase E activity were examined.

Methodological variables during analysis of in vivo cerebellar cyclic GMP, an indirect marker of nitric oxide release.

In light of the recent recognition of the physiological significance of nitric oxide, there is considerable interest in the methodological variables that can confound the results of the cerebellar cGMP analysis from in vivo experiments. In this study, using male Swiss Webster mice, the effect of such methodological variables as 1) weight of the animals; 2) tissue extraction procedures used in radioimmunoassay for cGMP; and 3) the commercial source of the assay kit on, harmaline-, pentylenetetrazole- or SNAP-induced increase in cerebellar cGMP in vivo were evaluated. Results indicate that mice in the 15- to 19-g weight range are most sensitive and best suited for in vivo drug effects on cerebellar cGMP.

Effect of cocaine on macromolecular syntheses and cell proliferation in cultured glial cells.

In the present study the effect of cocaine on thymidine, uridine and leucine incorporation was assessed in primary cortical glial and C6 glioma cells. Cocaine exposure for 24 h inhibited thymidine and uridine incorporation in cortical glial and C6 glioma cells. However, the effect of cocaine on uridine incorporation was less prominent compared to thymidine incorporation.

Chronic administration of a nitric oxide synthase inhibitor, N omega-nitro-L-arginine, and drug-induced increase in cerebellar cyclic GMP in vivo.

N omega-nitro-L-arginine (NG-nitro-L-arginine) is a potent nitric oxide synthase inhibitor which crosses the blood brain barrier and does not undergo extensive metabolism in vivo. In this study, effect of chronic pretreatment of N omega-nitro-L-arginine (75 mg/kg, i.p.

On the mechanism of the interaction of ketamine and halothane in vitro.

1. Electrically induced contraction of guinea pig ileum myenteric plexus-longitudinal muscle was inhibited by ketamine and halothane with IC50s of 2.1 x 10(-4) M and 1.

Effect of nitric oxide on mitogenesis and proliferation of cerebellar glial cells.

In the brain, nitric oxide (NO) has been identified as a messenger molecule and a mediator of excitatory amino acid-induced neurotoxicity. In this study, the effects of NO on serum-induced mitogenesis and cell proliferation of the cerebellar glial cells were assessed. NO-generating agent, S-nitroso-N-acetylpenicillamine (SNAP) increased intracellular cyclic guanosine monophosphate (cGMP) levels.

Selective involvement of kappa opioid and phencyclidine receptors in the analgesic and motor effects of dynorphin-A-(1-13)-Tyr-Leu-Phe-Asn-Gly-Pro.

Dynorphin A-(1-13)-Tyr-Leu-Phe-Asn-Gly-Pro (Dyn Ia; 1-8 nmol) injected intracerebroventricularly in the mouse produces two independent behavioral effects: (1) a norbinaltorphimine (kappa opioid antagonist)-reversible analgesia in the acetic acid-induced writhing test and (2) motor dysfunction characterized by wild running, pop-corn jumping, hindlimb jerking and barrel rolling and antagonized by the irreversible phencyclidine (PCP) and sigma (sigma) receptor antagonist, metaphit and the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists, dextromethorphan and ketamine. The specific involvement of the PCP receptor in the motor effects of Dyn Ia is supported by the direct competitive interaction of the peptide with the binding of [3H]MK-801 (Ki: 0.63 microM) and [3H]TCP (Ki: 4.

Intracerebroventricular administration of kappa-agonists induces convulsions in mice.

Intracerebroventricular (ICV) administration of kappa-agonists (PD 117302, U-50488H and U-69593) induced convulsions in a dose-related manner in mice. The dose at which 50% of animals convulsed (CD50) was in nmol ranges for all opioids. Among the opioids used, PD 117302 was the most potent convulsant.