The Pharmacodynamics of PK 11195 in Diazepam-Dependent Male and Female Rats

Sloan, Jewell W.; Wala, Elzbieta P.; Jing, Xin; Holtman, Joseph R.

doi:10.1016/s0091-3057(00)00239-2

Cited by 6 publications

(3 citation statements)

References 74 publications

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“…For example, female rats show greater "physical" withdrawal than male rats from pentobarbital (Suzuki et al, 1992) and methaqualone (Suzuki et al, 1988). Additionally, diazepam-dependent female rats, compared with diazepam-dependent male rats, showed more intense flumazenil-precipitated physical withdrawal and motivational withdrawal (i.e., vocalizations; Sloan et al, 2000).…”

Section: Sex Differences In Drug Abusementioning

confidence: 99%

Sex Differences in Animal Models: Focus on Addiction

Becker

Koob

2016

Pharmacological Reviews

619

446

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Section: Sex Differences In Drug Abusementioning

confidence: 99%

Sex Differences in Animal Models: Focus on Addiction

Becker

Koob

2016

Pharmacological Reviews

619

446

View full text Add to dashboard Cite

“… Sloan et al (2000) observed the sex differences in the number in seizures, respiratory rate and vocalization in rats which first had implanted diazepam and then underwent withdrawal precipitated with either with PK11195, a peripheral BZ antagonist, and/or flumazenil. Flumazenil induced higher withdrawal scores in females, also female rats vocalized significantly more than male rats; however, flumazenil tended to produce more tachypnoea in male than in female rats.…”

Section: Part I: Introduction Definitions and General Considerationsmentioning

confidence: 99%

Dependence, withdrawal and rebound of CNS drugs: an update and regulatory considerations for new drugs development

Lerner

Klein

2019

Brain Communications

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The purpose of this paper is to describe dependence and withdrawal phenomena related to CNS drugs discontinuation and to clarify issues related to the evaluation of clinical drug withdrawal and rebound as they relate to safety in new drug development (FDA Abuse Guidance 2017) (FDA, 2017). The paper presents current understanding and definitions of drug dependence and withdrawal which are also relevant and important features of addiction, though not the same. Addiction, called substance use disorder in DSM-5 (APA, 2013), affects an individual’s brain and behavior, represents uncontrollable drug abuse and inability to stop taking a drug regardless of the harm it causes. Characteristic withdrawal syndromes following abrupt discontinuation of CNS active drugs from numerous drug classes are described. These include drugs both scheduled and nonscheduled in the Controlled Substances Act, which categorizes drugs in five schedules based on their relative abuse potentials and dependence liabilities and for regulatory purposes (Congress, 1970). Schedules 1 and 2 contain drugs identified as those with the highest abuse potential and strictest regulations. Less recognized aspects of drug withdrawal, such as rebound and protracted withdrawal syndromes for several drug classes are also addressed. Part I presents relevant definitions and describes clinical withdrawal and dependence phenomena. Part II reviews known withdrawal syndromes for the different drug classes and describes rebound and protracted withdrawal syndromes. To our knowledge, this is the first compilation of withdrawal syndromes for CNS drugs. Part III provides details of evaluation of dependence and withdrawal in the clinical trials for CNS drugs, which includes general design recommendations, and several tools, such as withdrawal questionnaires and multiple scales that are helpful in the systematic evaluation of withdrawal. The limitations of different aspects of this method of dependence and withdrawal evaluation are also discussed.

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“…For intranasal dosing, drugs first encounter the nasal passageways and mucosal barriers, for which mucous pH, secretion, and clearance have been shown to be sex-dependent (England et al, 1999;Hallschmid, 2021;Luberti et al, 2021;Marjan, 2023). Additional sex differences have been observed for drug ADME through ocular (Nakamura et al, 2005), intravascular (Kunio et al, 2018), and subcutaneous (Sloan, 2000) dosing paradigms; physiological considerations for these parenteral routes of administration are reviewed elsewhere (Donovan, 2005).…”

Section: Physiological Basis For Sex Differences In Admementioning

confidence: 99%

Acute brain injury and nanomedicine: sex as a biological variable

Simmons,

Mihalek,

Bimonte Nelson

et al. 2024

Front. Biomater. Sci.

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Sex as a biological variable has been recognized for decades to be a critical aspect of the drug development process, as differences in drug pharmacology and toxicity in female versus male subjects can drive the success or failure of new therapeutics. These concepts in development of traditional drug systems have only recently begun to be applied for advancing nanomedicine systems that are designed for drug delivery or imaging in the central nervous system (CNS). This review provides a comprehensive overview of the current state of two fields of research - nanomedicine and acute brain injury—centering on sex as a biological variable. We highlight areas of each field that provide foundational understanding of sex as a biological variable in nanomedicine, brain development, immune response, and pathophysiology of traumatic brain injury and stroke. We describe current knowledge on female versus male physiology as well as a growing number of empirical reports that directly address sex as a biological variable in these contexts. In sum, the data make clear two key observations. First, the manner in which sex affects nanomedicine distribution, toxicity, or efficacy is important, complex, and depends on the specific nanoparticle system under considerations; second, although field knowledge is accumulating to enable us to understand sex as a biological variable in the fields of nanomedicine and acute brain injury, there are critical gaps in knowledge that will need to be addressed. We anticipate that understanding sex as a biological variable in the development of nanomedicine systems to treat acute CNS injury will be an important determinant of their success.

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The Pharmacodynamics of PK 11195 in Diazepam-Dependent Male and Female Rats

Cited by 6 publications

References 74 publications

Sex Differences in Animal Models: Focus on Addiction

Sex Differences in Animal Models: Focus on Addiction

Dependence, withdrawal and rebound of CNS drugs: an update and regulatory considerations for new drugs development

Acute brain injury and nanomedicine: sex as a biological variable

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