Abuse potential

Like mAChRs, nAChRs have been implicated in the etiology of ALheimef s disease and related dementias as well as in gastrointestinal and cardiovascular disorders. Nicotine has high abuse potential and is the primary component in reinforcing smoking behaviors. Nicotine patches have been... 

Pemoline [2152-34-3] (24), stmcturally dissimilar to amphetamine or methylphenidate, appears to share the CNS-stimulating properties. As a consequence, pemoline is employed in the treatment of ADHD and of narcolepsy. There are several other compounds that are stmcturally related to amphetamines, although not as potent and, presumably, without as much abuse potential. These compounds also have anorexic effects and are used to treat obesity. Some of the compounds available are phentermine [122-09-8] fenfluramine [458-24-2] and an agent that is available over-the-counter, phenylpropanolamine [1483815-4] (26). 

Compounds available in the United States are Hsted in Table 1. Whereas they vary in degree, all of them share similar HabiUties of cardiovascular side effects, the potential for central nervous system (CNS) stimulation, the development of tolerance, and abuse potential. AH, with the exception of ma2indol, are derivatives of phenethylamine. The introduction of an oxygen atom on the -carbon of the side chain tends to reduce CNS stimulant properties without decreasing the anorectic activity. Following the Federal Controlled Dmg Act of 1970, dmgs were classified into one of five schedules according to medical utiUty and abuse potential. 

Codeine, like morphine, is isolated from the opium poppy. However, the low yield of 0.7—2.5% does not provide sufficient material to meet commercial demands. The majority of marketed codeine is prepared by methylating the phenolic hydroxyl group of morphine. Morphine yields from opium poppy are 4—21%. When prescribed for cough, the usual oral dose is 10—20 mg, three to four times daily. At these doses, adverse side effects are very few. Although the abuse potential for codeine is relatively low, the compound can substitute for morphine in addicts (47). 

Cannabinoids were used in medicine in the form of their crude extracts many centuries ago. Lately the use of cannabis for so-called recreational purposes has become a national vice of substantial proportions. Several attempts have been made to focus the potentially useful pharmacological properties of marijuana into drug molecules with no abuse potential. 

Psychostimulants. Figure 3 Effect of methylphenidate depending on baseline tonic (T) and phasic (P) dopamine levels. In a normal state only minimal changes are noted (which points to a rather low abuse potential). From a hypoactive state, methylphenidate increases both Tand P levels. However, this is much more true for the strongly lowered P tone. In contrast, in moderately hyperactive states and ADHD, T levels are increased and P levels are decreased, respectively, correlating with the baseline levels (adapted from [2]). 

The Controlled Substances Act of 1970 regulates die manufacture, distribution, and dispensing of drugs that have abuse potential (see information under Federal Drag Legislation and Enforcement in diis chapter). Drag under the Controlled Substances Act are divided into five schedules, based on their potential for abuse and physical and psychological dependence Display 1-2 describes the five schedules. 

Less abuse potential than schedule II drugs... 

The CNS stimulants include the analeptics, drugs tiiat stimulate the respiratory center of the CNS the amphetamines, drugs witii a high abuse potential because of dieir ability to produce euphoria and wakefulness and the anorexiants, drugs used to suppress die appetite... 

Some antianxiety drug, such as buspirone (BuSpar), seem to have less abuse potential and less effect on motor ability and cognition than that of Hie other anfianxiety drug. 

The benzodiazepines currently available for clinical use vary substantially in pharmacokinetics, acute euphoriant effects, and frequency of reported dependence. It is likely, therefore, than not all benzodiazepines have the same potential for abuse. Diazepam, lorazepam, and alprazolam may have greater abuse potential than chlordiazepoxide and clorazepate (Wolf et al. 1990). Similarly, oxazepam has been reported to produce low levels of abuse (Eliding 1978). Jaffe et al. (1983) found that in recently detoxified alcoholic patients, halazepam produces minimal euphoria even at a supratherapeutic dosage. The development of partial agonist and mixed agonist/antagonist compounds at the benzodiazepine receptor complex may offer an advantage over approved benzodiazepines for use in alcoholic patients. 

Anxiolytics with little abuse potential, such as buspirone, and antidepressants that have a benign side-effect profile and may reduce ethanol intake warrant careful evaluation in the treatment of anxious and depressed alcoholic patients. 

Bliding A The abuse potential of benzodiazepines with special reference to oxazepam. Acta Psychiatr Scand Suppl 274 111-116, 1978... 

Iwata N, Cowley DS, Radel M, et al Relationship between a GABA alpha g Pro385Ser substitution and benzodiazepine sensitivity. Am] Psychiatry 156 1447—1449,1999 Jacobson AF, Dominguez RA, Goldstein B, et al Comparison of buspirone and diazepam in generalized anxiety disorder. Pharmacotherapy 5 290—296, 1985 Jaffe JH, Ciraulo DA, Nies A, et al Abuse potential of halazepam and diazepam in patients recently treated for acute alcohol withdrawal. Clin Pharmacol Ther 34 623-630, 1983... 

Jasinski DR, PevnickJS, Griffith JD Human pharmacology and abuse potential of the analgesic buprenorphine. Arch Gen Psychiatry 35 501-516, 1978 Jasinski DR, Johnson RE, Kocher TR Clonidine in morphine withdrawal differential effects on signs and symptoms. Arch Gen Psychiatry 42 1063-1066, 1983... 

Benzodiazepines and similar agents occupy a position of intermediate abuse potential, compared with most other sedative-hypnotics (Griffiths and Weerts 1997). Animal models of abuse habihty indicate that the reinforcing effects of benzodiazepines are less pronounced than are those of the barbiturates, opioids, and stimulants. Differences in abuse potential within the class have not been consistently demonstrated however, most chnicians agree that benzodiazepines with a rapid onset and short duration of action pose the greatest risk in susceptible individuals. 

Limited results from clinical laboratory evaluations suggested that the GABAj l agonists zaleplon (Rush et al. 1999b) and Zolpidem (Rush et al. 1999a) produce effects that are consistent with abuse potential comparable to that of the benzodiazepine triazolam. The reported incidence of dependence on Zolpidem in the medical literature is low, compared with that for benzodiazepines, and is characterized by use of high doses, often in individuals with a history of substance abuse (Hajak et al. 2003 Vartzopoulos et al. 2000). 

Jaffe JH, Ciraulo DA, Nies A, et al Abuse potential of halazepam and of diazepam in patients recently treated for acute alcohol withdrawal. Clin Pharmacol Ther 34 623-630, 1983... 

Because chronic cocaine use appears to reduce the efficiency of central dopamine neurotransmission, a number of dopaminergic compounds, including amantadine, bromocriptine, mazindol, and methylphenidate, have been examined as treatments for cocaine abuse. It is thought that these relatively slow-onset dopaminergic agents, with low or relatively low abuse potential, would correct the dopamine dysregulation and alleviate withdrawal symptoms following chronic stimulant use. 

Most of the motor effects of amphetamine, especially stereotypy, are due to the release of DA as are its psychotic effects such as hallucinations. Its ability to mimic the action of DA in reward and reinforcement behaviour may contribute to its abuse potential (see Chapter 22) but its arousal (stimulant) properties also involve NA release. 

The category risks to personnel and plant consists of two parts environmental abuse potential and occupational health/safety hazards and, here again, points are subtracted from a basic score for environmental/safety hazards. 

The process profile is presented as a bar chart, with a separate bar for each parameter. The width of each bar reflects the relative importance of a parameter s maximum impact. The bar chart highlights process strengths and weaknesses. This is illustrated in Fig. 2.7, which shows the process profile for 1. It is immediately apparent that the weakness of the process is. its environmental abuse potential. 

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