Dioxadrol

309.409

309.40

4D70V7R51N

30.5

3.4

In water, 19.2 mg/L at 25 °C (est)

8.26X10-8 mm Hg at 25 °C (est)

Henry's Law constant = 4.5X10-11 atm-cu m/mole at 25 °C (est)

Oily liquid /Dioxadrol/|Crystals from methanol, mp 256-260 °C /Dioxadrol hydrochloride/|Hydroxyl radical reaction rate constant = 1.29X10-10 atm-cu m/mole at 25 °C (est)

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

The interactions of phencyclidine (PCP) and related agonists with putative receptor blockers were studied on cerebellar Purkinje neurons using electrophysiological techniques. Depressions induced by PCP or dexoxadrol, a sigma receptor agonist, were markedly antagonized by the PCP receptor antagonist metaphit, which acylates PCP receptors via its isothiocyanate moiety. Conversely, the depressant effect of levoxadrol, the (-) isomer of dexoxadrol, was not affected by metaphit. Further evidence that metaphit's specific antagonism of dexoxadrol- and PCP-mediated depressions was derived from data showing that drugs which respectively acylate mu and delta opioid receptors, benzimidazole isothiocyanate and fentanyl isothiocyanate, do not antagonize the actions of either PCP or dexoxadrol. Moreover, tyramine, which like PCP acts as an indirect norepinephrine agonist, is not antagonized by metaphit. These observations support the concept that metaphit causes a pharmacologically specific and irreversible antagonism of the effects of both PCP and dexoxadrol in the cerebellum. ...|... Phencyclidine (PCP)-induced catalepsy in pigeons, which is a pharmacologically specific and stereoselective phenomenon, was used to study pharmacological consequences of the proposed covalent bonding of metaphit to PCP sites. Metaphit pretreatment increased the cataleptic effects induced by cumulative doses of PCP-type drugs (ie, PCP, ketamine and m-amino PCP) and of drugs that have PCP-like actions (i.e., dexoxadrol, LY 154716 and cyclazocine)...|The binding of [3H]phencyclidine (PCP) to receptors in rat brain cortex has been studied. Two receptors have been detected, a high affinity receptor site with a KD of 23.5 +/- 7.4 nM and a low affinity site with a KD of 7.6 +/- 1.8 microM. The binding of [3H]PCP to its receptors was pH and temperature dependent and was destroyed by heat-denaturation. The binding of [3H]PCP was inhibited by compounds which produce PCP-like behavioral effects including dexoxadrol, etoxadrol and ketamine as well as a novel series of benz(f)isoquinolines. The low affinity site was blocked by PCP, etoxadrol and (+)-SKF-10,047 but not morphine or leu-enkephalin, suggesting that it also represents a specific PCP site. Stereoselective displacement of PCP at the high affinity receptor was observed with the isomers of cyclazocine, cyclorphan, SKF-10,047 and dioxadrol (dexoxadrol and levoxadrol). Naloxone, 4,5,6,7-tetrahydroisoxazolo(S,4-C)pyridin-3-ol (THIP) hydrate and haloperidol inhibited binding poorly (Ki greater than 1 microM), suggesting that these compounds do not interact significantly with the high affinity PCP receptor in vivo. The affinity of ligands for the phencyclidine receptor was highly correlated (r = 0.714, P less than 0.01) with their potency to produce catalepsy in pigeons.

Compounds capable of relieving pain without the loss of CONSCIOUSNESS. (See all compounds classified as Analgesics.)

(3)H-Dexoxadrol, a dissociative anesthetic, binds with high affinity to specific sites in rat brain (membrane binding and light microscopic autoradiography). Various phencyclidine analogues compete for (3)H-dexoxadrol sites in a slightly different manner than against (3)H-phencyclidine binding sites. As for (3)H-phencyclidine binding, (3)H-dexoxadrol binding sites are highly concentrated in brain regions such as the cortex and the hippocampus. However, other areas such as the hypothalamus are enriched only in (3)H-dexoxadrol binding sites. This suggests that (3)H-dexoxadrol binds to phencyclidine-related sites in certain brain regions but not in others. In the human forebrain, (3)H-dexoxadrol binding sites are distributed as in the rat brain and mainly found in the caudate, putamen and cortex.

... Dexoxadrol, the D-isomer of dioxodrol, which produces phencyclidine (PCP)-like behavioral effects and displaces bound [3H]PCP, was a potent blocker of the PCP-sensitive, voltage-gated K+ channel. The corresponding L-isomer, levoxadrol, which produces morphine-like antinociception and sedation, but does not produce PCP-like behavior nor displace bound (3H)PCP, was a very weak blocker of the voltage-gated K+ channel. Levoxadrol, but not dexoxadrol, activated a separate K+ channel, as manifested by an increase in 86Rb /from synaptosomes prepared from rat forebrain/ efflux. This effect was blocked by naloxone. /It was concluded/ that one of the PCP-sigma-ligand binding sites in the brain may be associated with the voltage-gated, non-inactivating K+ channel ... observed in nerve terminals. /The/ findings are also consistent with the view that some of the behavioral manifestations of PCP intoxication are mediated by block of presynaptic K+ channels.

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/HUMAN EXPOSURE STUDIES/ In nine subjects representing a majority (75 percent) of the population tested, ten milligrams of Dexoxadrol combined with 600 mg of acetylsalicylic acid (ASA) was essentially equivalent to 20 or 30 mg of Dexoxadrol pooled sample when tested by ischemic arm method, both doses being significantly more potent than ASA alone one hour after dosage. Three hours after dosage, all doses of Dexoxadrol were still significantly above ASA alone or lactose placebo indicating a more prolonged action of this drug. The stimulating effect of lactose placebo is postulated to explain the temporary rise (1 hr) noted by use of this substance. When all twelve subjects are considered, because of three negative reactors, only statistically significant differences between ten milligrams of Dexoxadrol plus 600 mg of ASA are distinguishable from ASA alone or placebo at the end of one hour. At all dosage levels some side effects similar to alcohol were noted, numbness, dizziness, drowsiness, etc. ... The 30 and 20 mg dosage produced more prominent psychic effects, while the 10 mg dosage with ASA produced a minimum of such effects and was virtually as effective as the higher dosage in nine of twelve subjects.

2-(2,2-diphenyl-1,3-dioxolan-4-yl)piperidine

... Dioxadrol can be resolved into two enantiomers, dexoxadrol /the d-isomer/ and levoxadrol /the l-isomer/ ...