Pipradrol

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 9000(SRC), determined from a structure estimation method(2), indicates that pipradrol is expected to be immobile in soil(SRC). The estimated pKa of pipradrol is 9.95(3), indicating that this compound will exist almost entirely in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization from moist soil is not expected because the compound exists as a cation and cations do not volatilize. Pipradrol is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.1X10-8 mm Hg at 25 °C(SRC), determined from a fragment constant method(5). Biodegradation data in soil were not available(SRC, 2012).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 9000(SRC), determined from a structure estimation method(2), indicates that pipradrol is expected to adsorb to suspended solids and sediment(SRC). An estimated pKa of 9.95(3) indicates pipradrol will exist almost entirely in the cation form at pH values of 5 to 9 and therefore volatilization from water surfaces is not expected to be an important fate process(SRC). According to a classification scheme(4), an estimated BCF of 87(SRC), from an estimated log Kow of 2.45(5) and a regression-derived equation(6), suggests the potential for bioconcentration in aquatic organisms is moderate(SRC). Biodegradation data in water were not available(SRC, 2012).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), pipradrol, which has an estimated vapor pressure of 1.1X10-8 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase pipradrol is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 0.75 hours(SRC), calculated from its rate constant of 1.7X10-10 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase pipradrol may be removed from the air by wet or dry deposition(SRC). Pipradrol does not contain chromophores that absorb at wavelengths >290 nm(4), and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of pipradrol can be estimated to be 9000(SRC). According to a classification scheme(2), this estimated Koc value suggests that pipradrol is expected to be immobile in soil. The estimated pKa of pipradrol is 9.95(3), indicating that this compound will exist almost entirely in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4).

An estimated BCF of 87 was calculated in fish for pipradrol(SRC), using an estimated log Kow of 3.45(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is moderate(SRC).

An estimated pKa of 9.95(1) indicates pipradrol will exist almost entirely in the cation form at pH values of 5 to 9 and therefore volatilization from water surfaces is not expected to be an important fate process. Pipradrol is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.1X10-8 mm Hg(SRC), determined from a fragment constant method(3).

/LABORATORY ANIMALS: Acute Exposure/ Under the influence of prolonged muscular work (swimming for 5 hours) the content of ATP, ADP, AMP, and creatine phosphate in the brain of albino rats was reduced, while anaerobic carbohydrate breakdown was intensified. The lowered concentration of high-energy-phosphates was due to a deficiency of their resynthesis because of disturbance of the coupling of oxidative phosphorylation and of the integrity of the mitochondrial membranes. Administration of pipradrol to the rats before swimming led to more severe disturbances of oxidative brain metabolism, reduced the generation of high-energy phosphates, and thus evidently lead to exhaustion of the energy reserves of the brain.

/LABORATORY ANIMALS: Acute Exposure/ Intravenous administration of the stimulant drug pipradrol evoked a dose-dependent hyperthermic response in rabbits. This drug effect was significantly reduced by pretreatment with chlorpromazine, phenoxybenzamine, intravenous BE-2254 or intracerebroventricular BE-2254. In animals pretreated with cyproheptadine or atropine, the hyperthermic effect was significantly potentiated. However, haloperidol, pimozide, diphenhydramine and pentobarbital failed to appreciably influence the drug response. These findings suggest that pipradrol-induced hyperthermia in the rabbit involves activation of central alpha-adrenergic receptors and is apparently enhanced by blockade of serotonergic or cholinergic receptors

/BEHAVIORAL STUDIES/ The shuttlebox self-stimulation test is claimed by Atrens to differentiate drug effects on brain stimulation reward from those on performance variables. Thus, for example, drug-induced enhancement of the reward value of stimulation should be reflected in a selective reduction of the latency to initiate stimulation (the ON latency), as compared with the latency to terminate stimulation (the OFF latency). The effects of the psychostimulant drugs, d-amphetamine and pipradrol, and the antidepressant, bupropion, were evaluated in this procedure as well as in a bar-pressing test of self-stimulation. Pipradrol (3 and 10 mg/kg) and bupropion (54 mg/kg) reduced ON latencies by 40% or more but failed to shorten OFF latencies, indicating that performance variables were not involved in the ON latency decrements. Although d-amphetamine (0.3 and 1.0 mg/kg) shortened ON latencies, the 1.0 mg/kg dose also reduced OFF latencies. Drug doses that reduced ON latencies also increased bar-pressing self-stimulation. The shuttlebox self-stimulation test appears to be capable of discriminating drug-induced enhancement in brain stimulation reward from performance variables.

/BEHAVIORAL STUDIES/ The hypothesis that a psychomotor stimulant drug (pipradrol) enhances the reinforcing effects of stimuli paired with reinforcing brain stimulation was tested using a conditioned reinforcement paradigm. Rats were trained to discriminate between two stimuli (S+ and S-) to obtain /intracranial stimulation (ICS)/ in the lateral hypothalamus by pushing a panel in the presence of S+. In a subsequent preference test, ICS was no longer available, but responding on one of two novel levers now produced S+, whereas responding on the other lever produced S-. Four groups of four rats received 0, 5, 10 or 15 mg/kg pipradrol. Doses of 5 and 10 mg/kg significantly enhanced the preference for S+ over S-. These doses increased responding for S+, but had no effect on responding for S-. These results support the hypothesis tested, and suggest that pipradrol potentiates the effects of conditioned reinforcement.

For more Non-Human Toxicity Excerpts (Complete) data for Pipradrol (8 total), please visit the HSDB record page.

The rate constant for the vapor-phase reaction of pipradrol with photochemically-produced hydroxyl radicals has been estimated as 1.7X10-10 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 0.75 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). Pipradrol is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(3). Pipradrol does not contain chromophores that absorb at wavelengths >290 nm(3), and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).

While data specific to pipradrol were not located(SRC, 2012), the literature suggests that some pharmaceutically active compounds originating from human and veterinary therapy are not eliminated completely in municipal sewage treatment plants and are therefore discharged into receiving waters(1). Wastewater treatment processes often were not designed to remove them from the effluent(2). Selected organic waste compounds may be degrading to new and more persistent compounds that may be released instead of or in addition to the parent compound(2). Studies have indicated that several polar pharmaceutically active compounds can leach through soils(1).

Pipradrol's production and use in biochemical research and illegal drug of abuse may result in its release to the environment through various waste streams. If released to air, an estimated vapor pressure of 1.1X10-8 mm Hg at 25 °C indicates pipradrol will exist in both the vapor and particulate phases in the atmosphere. Vapor-phase pipradrol will be degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals; the half-life for this reaction in air is estimated to be 0.75 hours. Particulate-phase pipradrol will be removed from the atmosphere by wet or dry deposition. Pipradrol does not contain chromophores that absorb at wavelengths >290 nm, and therefore is not expected to be susceptible to direct photolysis by sunlight. If released to soil, pipradrol is expected to have no mobility based upon an estimated Koc of 9000. The estimated pKa of pipradrol is 9.95, indicating that this compound will exist almost entirely in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts. Pipradrol may volatilize from dry soil surfaces based upon its vapor pressure. Biodegradation data were not available. If released into water, pipradrol is expected to adsorb to suspended solids and sediment based upon the estimated Koc. The estimated pKa indicates pipradrol will exist almost entirely in the cation form at pH values of 5 to 9 and therefore volatilization from water surfaces is not expected to be an important fate process. An estimated BCF of 87 suggests the potential for bioconcentration in aquatic organisms is moderate. Hydrolysis is not expected to be an important environmental fate process since this compound lacks functional groups that hydrolyze under environmental conditions (pH 5 to 9). Occupational exposure to pipradrol may occur through dermal contact with this compound at workplaces where pipradrol is produced or used. Limited general population exposure to pipradrol will be through illegal use of the drug. (SRC)

Rapidly absorbed.

Quickly excreted in the urine (3.5%) and stool (5%).

Distributed in the liver, kidney and brain tissue.

Rapidly cleared.