Morphine dependence potential

Side-effect profile The compound has a morphine-type abuse and dependence potential. 

Side-effects Hydrocodone induces side-effects similar to codeine and morphine and has an appreciable abuse and dependence potential (Morrison, 1979). 

Side-effects Ketobemidone has morphine-like side-effect and a similar abuse and dependence potential. 

Side-effects Oxycodone has a morphine-like side-effect profile. Respiratory depression has been found in children. The compound has a relevant abuse and dependence potential and illicit use of the retarded preparations has been reported. 

Antkiewicz-Michaluk, L., Michaluk, J., Romanska, I., Vetulani, J. Reduction of morphine dependence and potentiation of analgesia by chronic co-administration of nifedipine, Psychopharmacology 1993, 111, 457-464. 

Pentazocine, although two to three times weaker as an analgetic than morphine, became useful because of its extremely low dependence potential. It does, however, share some of morphine s undesirable side effects, particularly respiratory embarrassment in the upper therapeutic dosage ranges. At single doses of 60 mg or more the dysphoric and hallucinogenic effects first noticed with nalorphine also become apparent with pentazocine. These are reversible with naloxone (but not nalorphine). 

Schedule 11 drugs have an accepted medical use in the United States and a high rate of abuse, with either severe psychological or physical dependence potential. These drugs include morphine, codeine, cocaine, amphetamine, and most barbiturate preparations containing amobarbital, secobarbital, and pentobarbital. 

The three prototype mixed p agonist/S antagonists described in this chapter have excellent potential as analgesics with low propensity to produce tolerance and dependence. The pseudotetrapeptide DIPP-NH2[ ] has already been shown to produce a potent analgesic effect, less tolerance than morphine, and no physical dependence upon chronic administration. In preliminary experiments, the tetrapeptides DIPP-NH2 and DIPP-NH2[T] were shown to cross the BBB to some extent, but further structural modifications need to be performed in order to improve the BBB penetration of these compounds. The Tyr-Tic dipeptide derivatives can also be expected to penetrate into the central nervous system because they are relatively small, lipophilic molecules. In this context, it is of interest to point out that the structurally related dipeptide H-Dmt-D-Ala-NH-(CH2)3-Ph (SC-39566), a plain p-opioid agonist, produced antinociception in the rat by subcutaneous and oral administration [72], As indicated by the results of the NMR and molecular mechanics studies, the conformation of the cyclic p-casomorphin analogue H-Tyr-c[-D-Orn-2-Nal-D-Pro-Gly-] is stabilized by intramolecular hydrogen bonds. There-... 

Gaillard, P. Carrupt, P.-A. Testa, B., The conformation-dependent lipophilicity of morphine glucuronides as calculated from the molecular lipophilicity potential, Bioorg. Med. Chem. Lett. 4, 737-742 (1994). 

This class produces analgesia and has a ceiling effect on respiratory depression and lower abuse potential than morphine. However, psychotomimetic responses (e.g., hallucinations and dysphoria with pentazocine), a ceiling analgesic effect, and the propensity to initiate withdrawal in opioid-dependent patients have limited their widespread use. 

Schedule II—The drug or other substance has (1) a high potential for abuse, (2) a currently accepted medical use in treatment in the United States or a currently accepted medical use with severe restrictions, and (3) abuse of the drug or other substances may lead to severe psychological or physical dependence. Examples cocaine, PCP, morphine, fentanyl and meperidine, codeine, amphetamine and methamphetamine, Ritalin . 

Ibogaine itself stimulates locomotor activity in rats. However, it reduces the locomotor activity induced by morphine, with greater effects in female animals than males (Pearl et al. 1997). It also reduces locomotor activity induced by cocaine and amphetamine (Sershen et al. 1992a, 1992b Blackburn and Szumlinski 1997). However, the interaction between ibogaine and cocaine is time-dependent, with motor activity inhibited at short delays, but potentiated at long delays (Maisonneuve et al. 1997). 

Morphine and other opiates are powerful analgesics but have dependency and abuse potential. 

---