Dependence liability

Dependence liability Dephlegmators Dephosphorization Depilatories Depitching... 

Reynaud M, Petit G, Potard D, et al Six deaths linked to concomitant use of buprenor-phine and benzodiazepines. Addiction 93 1383-1392, 1998 Richards JG, Martin JR Binding profiles and physical dependence liabilities of selected benzodiazepine receptor ligands. Brain Res Bull 43 381-387, 1998... 

Until recently, d-fenfiuramine was used to control appetite, in preference to d-amphetamine, because it has a lower affinity for the catecholamine transporter and so its uptake into noradrenergic and dopaminergic neurons is much less than that of amphetamine. This is thought to explain why, at anorectic doses, this compound lacks the psychotropic effects and dependence-liability that are real problems with if-amphetamine. Unfortunately, despite this therapeutic advantage, this compound has had to be withdrawn from the clinic because of worries that it might cause primary pulmonary hypertension, valvular heart disease and even long-term neuropathy. 

Similarly, self-administration of MDMA in monkeys trained to self-administer amphetamine (Kamien et al. 1986) or in monkeys or baboons trained to self-administer cocaine (Beardsley et al. 1986 Lamb and Griffiths 1987) probably reflects a dopaminergic component to the pharmacology of MDMA. This would be consistent with current theories of dopamine involvement in the mechanism of action of drugs with dependence liability (Wise and Bozarth 1987). 

My own bias is toward the therapeutic potential. I do not care whether anything we develop produces euphoria or dependence potential. I think from the point of view of a drug abuse problem or a dependence liability that the alpha-ethyl probably does not have the reinforcing qualities and is not as pleasurable as MDMA. 

These differences in the behavioural properties of the opioid receptor sub-types are of considerable interest because the clinical use of currently marketed opioid analgesic drugs is limited by their undesirable side-effects, which include respiratory depression, constipation and an abuse or dependence liability. These side-effects have been associated with mu receptor ac-... 

Schedule II (c-/7) - High abuse potential with severe dependence liability (eg, narcotics, amphetamines, dronabinol, some barbiturates). 

Schedule III c-iii) - Less abuse potential than schedule II drugs and moderate dependence liability (eg, nonbarbiturate sedatives, nonamphetamine stimulants, limited amounts of certain narcotics). 

The opioids block cough by a mechanism that is not yet understood. No stereoselectivity of the opioids for blockade of the cough reflex has been shown. Thus, the isomers of opioids, such as dextrorphan, are as efficacious as the L-isomers as antitussives. This lack of stereoselectivity prompted the development of the D-isomers of opioids as antitussives since they are devoid of the dependence liability of h-isomers. Drugs with predominantly antitussive effects are described later in this chapter. Certain of the opioids, such as propoxyphene and meperidine, are relatively devoid of antitussive effects. 

It is a pure antagonist and chemically related to naloxone. It is more potent than naloxone and because of its longer duration of action, it can be used as maintenance drug for morphine addicts. It has no euphoric effect and no physical dependence liability. It is effective orally. It is also claimed to be beneficial in decreasing craving for alcohol in alcoholics. Side effects include gastrointestinal disturbances and muscular pain. 

Catalytic hydrogenation of the hydrolysis product leads to the orally active compound oxycodenone (7-1), which is used in a number of analgesic drugs. Cleavage of the methyl ether to the free phenol leads to one of the most potent close analogues of morphine, oxymorphone (7-2) [5]. Note that both of these compounds carry the hazards of classical opiate dependence liability. 

Negus SS Woods JH (1995). Reinforcing effects, discriminative stimulus effects, and physical dependence liability of buprenorphine. In Cowan A Lewis JW (eds.) Buprenorphine Combatting Drug Abuse with a Unique Opioid. New York Wiley-Liss, pp. 71-101... 

Two studies have indicated that the tricyclic antidepressant (TCA) imipramine may be as effective as BZDs in the treatment of GAD ( 58, 59). No studies longer than 8 weeks duration have been conducted, however, and imipramine s onset of anxiolytic action may be even slower than that of buspirone. Aithough adverse effects also may limit usefulness, its lack of dependence liability may make it an appropriate alternative in chronically anxious patients who also suffer from panic and depression. 

Half-lives from 2-40 h oral activity Hepatic metabolism-some active metabolites Toxicity Extensions of CNS depressant effects dependence liability Interactions Additive CNS depression with ethanol and many other drugs... 

Eszopiclone Bind selectively to a subgroup of GABAa receptors, acting like benzodiazepines to enhance membrane hyperpolarization Rapid onset of hypnosis with few amnestic effects or day-after psychomotor depression or somnolence Sleep disorders, especially those characterized by difficulty in falling asleep Oral activity short half-lives CYP substrates Toxicity Extensions of CNS depressant effects dependence liability Interactions Additive CNS depression with ethanol and many other drugs... 

The earliest attempts to develop a non-dependence-inducing morphine derivative resulted in the preparation of heroin (3,6-diacetylmorphine) by acetylation of morphine (Wright, 1874, Dreser, 1898). The potency of heroin was soon recognized. It underwent more investigation than any other product of the time, and was introduced into clinical medicine in 1898. Reports of its reduced respiratory depression and dependence liability were soon shown to be unfounded, but its analgesic effects in animals and man (twice morphine) were confirmed. Pharmacological examination of acyl derivatives of morphine showed that... 

After 10 years of intensive research, no significant dissociation of potent analgesia and dependence liability was accomplished. As an indirect result of the systematic program the identification of the 17-hydroxy-7,8-dihydro compounds oxycodone (patented in 1925 by E. Merck AG, Germany) and oxymorphone, derived from thebaine, are of particular note. 

Brogden, R.N., Speight, T.M., Avery, G.S. Pentazocine a review of its pharmacological properties, therapeutic efficacy and dependence liability, Drugs 1973, 5, 6-91. 

Dependence liability Dephlegmators Dephosphonzation Depilatories Depitchmg... 

Howes, J.F., A simple, reliable method for predicting the physical dependence liability of narcotic antagonist analgesics in the rat, Pharmacol. Biochem. Behav., 14, 689, 1981. 

Dorian P, Sellers EM, Kaplan H (1983) Evaluation of zopiclone physical dependence liability in normal volunteers. Pharmacology 27, Suppl 2 228-234... 

---