This document summarizes several newer narcotics and drugs of abuse, including their mechanisms of action, uses, and health effects. It discusses dextropropoxyphene (Darvon), an opioid pain reliever that is addictive and causes dependence. It also covers buprenorphine, used to treat opioid addiction, ketamine and PCP which are dissociative anesthetics, and LSD, mescaline and psilocybin which are hallucinogenic. Finally, it provides information on cannabinoids like THC, GHB, and several opioid antagonists such as nalbuphine, dezocine, naltrexone, and nalmefene.

1. NEWER NARCOTICS Cont.
S. Parasuraman M.Pharm., Ph.D.,
Senior Lecturer, Faculty of Pharmacy,
AIMST University,
Bedong 08100, Malaysia.

2. Propoxyphene
(Dextropropoxyphene; Darvon)
• Dextropropoxyphene is an optical isomer of
levopropoxyphene.
• It is act as mu-opioid receptor agonist, noncompetitive
α3β4 neuronal nicotinic acetylcholine receptor antagonist
and weak serotonin reuptake inhibitor.
• It has antitussive, local anaesthetic properties and used
to treat restless legs syndrome.
• Dextropropoxyphene is a weak opioid like codeine and
know to cause dependency among recreational users.
• Dextropropoxyphene is contraindicated in patients
allergic to paracetamol.

3. Propoxyphene
(Dextropropoxyphene; Darvon)
• Street names: Dillies, yellow footballs, and D.
• Adverse health effects of dextropropoxyphene abuse:
– Excessive opioid receptor stimulation may cause CNS
depression, respiratory depression, aspiration pneumonia,
miosis, and gastrointestinal effects. It may also account for
mood- or thought-altering effects.
– Both propoxyphene and its metabolite norpropoxyphene have
local anesthetic effects. Norpropoxyphene is a more potent local
anesthetic than propoxyphene, and they are both more potent
than lidocaine and blocks the sodium channels in cardiac
membrane.
– The local anesthetic effect propoxyphene, and
norpropoxyphene is responsible for arrhythmias and
cardiovascular depression seen in propoxyphene poisoning.

4. Propoxyphene
(Dextropropoxyphene; Darvon)
• Adverse health effects of dextropropoxyphene abuse:
– Both propoxyphene and norpropoxyphene toxic effects are not
reversed by naloxone.
– Balance disorder (risk of falls from standing height) is possible
event with propoxyphene.
– Symptoms of addiction:
• Delusions of grandeur with extended period of sleep is an sign of
addiction.
• Development of drug seeking behaviour.
– Addiction Treatment
• It is not potent pain killer, but highly addictive in nature.
• Physical addiction treated by Tapering method.
• Psychological addictions are secondary to the physical addiction and
subject may have withdrawal symptoms.
– The FDA not recommending use of propoxyphene as an
analgesics.

5. Buprenorphine (Temgesic)
• Buprenorphine is a semisynthetic opioid derivative of
thebaine.
• It is act as mixed agonist–antagonist opioid receptor
modulator which helps to
– opioid addiction in higher dosages
– control moderate acute pain in non-opioid-tolerant individuals in
lower dosages
– control moderate chronic pain in even smaller doses
• Use: Both buprenorphine and methadone are used for
detoxification in short- and long-term opioid replacement
therapy. The effectiveness of buprenorphine and methadone
are almost identical but except sedation. Methadone use to
produce more sedative effects than buprenorphine.

6. Buprenorphine (Temgesic)
• Abuse: Recreational users has stimulant effect and less of a
‘high’ effect than most opiates.
• Withdrawal: Withdrawal from buprenorphine can be severe
and generally should only occur under direct medical
attention. But withdrawal from methadone is considered
more severe and difficult to overcome.

7. Ketamine & Phencyclidine (PCP)
• Ketamine is a club drug, considered a dissociative
anesthetic agent.
• It s a NMDA receptor antagonist, but it also acts in an
opioid receptors and a monoamine transporters system.
• Street names: Angel dust, Hog, Special K, Ket, Kit kat,
Green K, Honey oil, Jet, Purple, Special la coke, Super
acid, Super C.
• Use: Anesthetic agent, antidepressant, sedation in
intensive care, pain killer, used in the treatment of
bronchospasm and complex regional pain syndrome.

8. Ketamine & Phencyclidine (PCP)
• Recreational use: ketamine is short acting, and produce
desired effect in 10 min and effects last 6in 60 min.
• At high doses unpleasant out-of-body and near-death
experiences have been reported.
• Ketamine do not cause dependence and addiction.
• In chronic exposure, particularly to PCP (primary care
provider), may lead to long-lasting psychosis closely
resembling schizophrenia.

9. LSD, Mescaline & Psilocybin

10. LSD, Mescaline & Psilocybin
• LSD, Mescaline & Psilocybin are commonly called
as hallucinogens.
• Lysergic acid diethylamide (LSD/ lysergide) is well
known psychedelic drug.
• Psilocybin and mescaline have been used for over
1000 years by native peoples on both continents
of the Americas. The active compound found in
organic sources of hallucinogens are alkaloids
that closely resemble the chemical structure of
brain chemicals like the neurotransmitter
seratonin, binding to seratonin receptor sites in
the brain.

11. LSD, Mescaline & Psilocybin

12. Cannabinoids
• Over 480 natural components found within the
Cannabis sativa plant, of which 66 have been
classified as "cannabinoids. In that delta-9-
tetrahydrocannabinol (Δ9-THC), is the substance
primarily responsible for the psychoactive effects of
cannabis.
• Cannabinoids mainly act on CB1 and CB2 receptor.
CB1 receptors are found primarily in the brain and
CB2 receptors are predominantly found in the
immune system.

13. Cannabinoids
• Endogenous cannabinoids such as 2-arachidonoyl
glycerol (2-AG) and anandamide are act as
neurotransmitter in CNS (CB1 receptors). These are
released at the postsynaptic somatodendritic
membrane and diffuse through the extracellular
space to bind at presynaptic CB1 receptors where
they inhibit the release of either glutamate or GABA.

14. Cannabinoids
• Exogenous cannabinoids such as D9 -
tetrahydrocannabinol (THC) are powerful
psychoactive substance, mainly inhibiting by
presynaptic GABA activity in VTA (Ventral Tegmental
Area).
• In high doses may result in visual hallucinations,
depersonalization and Frank psychotic (schizphrenia)
episodes.

15. Gamma-
hydroxybutyric acid
(GHB)
•GHB is an endogenous substance
produced during the metabolism of
GABA.
•First synthesized in 1960 and
introduced as a general anaesthetic
agent.
•It is club drug
•Street name: liquid ecstasy, grievous
bodily harm, date rape drug.
Nalbuphine • It is a mixed agonist–antagonist that is
similar in structure to both the
antagonist naloxone and the agonist
oxymorphone.
•High doses are perceived by addicts as
being like those of the barbiturates.

16. Dezocine (Dalgan) •It is a synthetic amino-tetralin
derivative with potent agonist–
antagonist effects.
Naltrexone (Trexan) •It is three to five times as potent as
naloxone and has a duration of action
of 24 to 72 hours, depending on the
dose.
•Naltrexone is orally active drug, and
has subjective effects of abused opioids
•It is used to decrease the craving for
opioids in highly motivated recovering
addicts.
•high doses of the opioids can
overcome the naltrexone blockade and
lead to seizures or respiratory
depression and death.

17. Nalmefene
• Nalmefene/ nalmetrene, is an opioid receptor antagonist
developed in the early 1970s, used primarily in the
management of alcohol dependence.
• It is a long-acting injectable pure opioid antagonist, bind all
opioid receptors and reverses the effects of opioid agonists
at those receptors.
• The onset of action is 2 minutes after IV administration.
• Hepatic metabolism is slow and occurs via glucuronide
conjugation to inactive metabolites.
• Its half-life of 11 hours is about 5 times that of naloxone.
• Indications include use in postoperative settings to reverse
respiratory depression and in opioid overdose.

18. Thank you