AIMTo design and synthesize new chiral 8-(substituted) amino-analogues of 3-[(tetrahydro-2-furanyl)methyl] benzomorphans, to expand knowledge of the structure-activity relationship (SAR) for 8-aminobenzomorphan.

METHODSTarget compounds were synthesized from the 8-triflate of the optically active 3-[(tetrahydro-2-furanyl)methyl]-2,6-methano-benzomorphans using Pd-catalyzed aminations. Opioid receptor binding experiments were performed to evaluate their biological activities.

RESULTSBoth 8-amino and 8-phenylamino analogues showed lower binding affinity for mu, delta and kappa receptors than corresponding 8-hydroxy-3-[(tetrahydro-2-furanyl)methyl]-2,6-methano-benzomorphan in vitro.

CONCLUSIONThe relative poor binding affinity of the target compounds did not warrant conducting the in vivo studies to determine if they have the profile(kappa agonist/mu antagonist) that will be potentially useful in the treatment of drug addiction. Further study is in progress.

Animals ; Benzomorphans ; chemical synthesis ; chemistry ; pharmacology ; Brain ; metabolism ; Furans ; chemical synthesis ; chemistry ; pharmacology ; Guinea Pigs ; Molecular Structure ; Narcotic Antagonists ; chemical synthesis ; chemistry ; pharmacology ; Radioligand Assay ; Receptors, Opioid ; metabolism ; Receptors, Opioid, delta ; metabolism ; Receptors, Opioid, kappa ; metabolism ; Receptors, Opioid, mu ; metabolism ; Structure-Activity Relationship

Disorders of sexual development are congenital in nature. Complete androgen insensitivity syndrome (CAIS) is a rare disorder with an incidence of nearly 1 in 20,000 male births. The majority of patients present with complaints of primary amenorrhoea and are phenotypically female but genotypically male. We report a case of a 40-year-old female presenting with backache and skin ulcers who was found to have exogenous Cushing’s syndrome with long glucocorticoid administration and suspected CAIS. The ulcers were secondary to intramuscular pentazocine injections.
Pentazocine ; Osteoporosis ; Pituitary ACTH Hypersecretion

The analgesic effect of epidural pentazocine for the postoperative pain relief was studied. In our previous report, we used the pentazocine diluted to normal saline, however in this study, pentazocine was diluted with distilled water and made to 10ml mixture. Fourty patients were divided into four groups (n=10) as follows: Group I: control, distilled water of 10 ml, Group II: pentazocine 0.2 mg/kg, Group III: pentazocine 0. 3mg/kg, Group IV: pentazocine 0.4mg/kg, all pentazocine groups were diluted to 10ml of distilled water. We have carried out the study to see the effects on the time of peak analgesia, the duration of analgesia, the degree of analgesia and the side effects. The results are as follows: 1) Seven cases (70%) in the control group showed rapid but short duration of analgesia. 2) The pentazocine 0.3 and 0.4 mg/kg groups were significantly different from the control group (p< 0.05). 3) In the pentazocine 0.3 and 0.4 mg/kg groups, the time of peak analgesia occured 8-9 minutes, the duration of analgesia was 10 hours and the degree of analgesia showed moderate to good degree. 4) Nine cases (90%) in the control group complained of back pain during epidural injection and 16 cases (53%) in the pentazocine group conplained of drowsiness.
Analgesia ; Back Pain ; Humans ; Injections, Epidural ; Pain, Postoperative* ; Pentazocine* ; Sleep Stages ; Water

Sedative and antiemetic effect of hydroxyzine as a premedicant were studied and results were compared with a placebo and Talwin. Two hundred and fourty patients were evaluated. These patients were divided into 6 groups. There were fourty patients in each group. Group 1: Hydroxyzine 50mg. Group 2: Hydroxyzine 100mg. Group 3: Placebo. Group 4: Talwin 20mg. Group 5: Hydroxyzine 5pmg plus Talwie 20mg. Group 6: Hydroxyzine 100mg plus Talwin 20mg. The results were as follows; 1) Satisfactory sedation was ovtained in 75% with group I, in 92.5% with group 2, in 30% with group 3, in 40% with group 4, in 82. 5% With group 5, and in 97. 5% with group 6. Better results were obtained with hydroxyzine plus Talwin group than hydroxyzine anly. 2) The incidence of postoperative nausea and vomiting in recovery room, 7. 5% wlth group 7. 5 % with group 3, 20% with group 4, 5%. with group 5. There was no case of nausea and vomiting in group 2 and group 6. We obtained a significant difference in antiemetic effect between Talwin only and the Talwin plus hydroxyzine group. 3) There was no adverse change on vital signs in all cases.
Antiemetics ; Humans ; Hydroxyzine* ; Incidence ; Nausea ; Pentazocine ; Postoperative Nausea and Vomiting ; Recovery Room ; Vital Signs ; Vomiting

Since intsaspinal morphine and demerol anesthesia have been reported we have noted anesthetic effects from the intraspinal nareotic injection. However, intraspinal mophine anesthesia appeared to cause prolonged respiratory depression with a slow onset and a very long duration which is not suitable for short surgical procedures. On the other hand, demerol or pentazocine were found to have a very short onset and duration with excellent local anesthetic effects. This study was primarily an attempt to take advantage of the rapid onset and short duration of demerol and pentazocine for simple and short surgical procedures. We had 43 cases scheduled for surgeries in the saddle ares i.e. hemorrhoidectomy, T.U.R., radium appli cator insertion and vaginal hysterectomy. All operations were performed under intraspinal demerol or pentazocine anesthesia, witch was satisfactory and the following results were obtained: 1) intraspinal dosage of demerol was 50mg or pentazocine was 30mg ofr hemorrhoidectomy, radium applicator insertion and T.U.R. For vaginal hysterectomy, the dosage was increased to 75mg~100mg for with demerol or 45mg with pentazocine. 2) Both analgesic effects apeeared from 1~2minutes after intraspinal injection and lasted 2 hours. 3) Mild somnolences were observed occasionally but no respiratory depression was seen. 4) Hemodynamics were stable throughout the entire procedures as well as postoperatively. 5) We came to the conclusion that a saddle block induced by intraspinal demerol or pentazocine injection was quite satisfactory in anesthesia practice for perineal surgery.
Anesthesia ; Anesthetics ; Female ; Hand ; Hemodynamics ; Hemorrhoidectomy ; Hysterectomy, Vaginal ; Injections, Spinal ; Meperidine ; Morphine ; Pentazocine ; Radium ; Respiratory Insufficiency

A number of recent reports haTe described the usefulness of the epidural injection of narcotics for the relief of postpoerative pain. But the epidural or intrathecal uke of a narcotic agonist-antagonist, especially one with a high lipid solubility such as penta97cine, has not been reported. The present studr was undertaken to evaluate the feasibility of pentagocine as an agent for postoperative pain relief when injected epidurally. 80 patients involved in this study were divided raadomlr into four groups: 10 ml saline (group 1, n=20); 0.2 mg/kg pentazocine in 10m1 saline(group 2, n=20): 0.3mg/kg penta- zocine in 10 ml saline(group 3, R= 20) ; 0.4 mg/kg pentazocine in 10 ml(group 4, n=20). she results were as follows : 1) 20(100%) patients from the 0.2 mg pentazocine group, 18(90%) form the 0.3mg/kg pentazocine group and 20(100%) from the 0.4 mg/kg pentazocine group obtained analgesic effects following the epidural injection of pentagzocine. 2) The peak analgesic effect following epidural pentafocine ocurred at 15 min(mean val-ue). 3) The duration of analgesia following epidural pentazocine ranged from 6 to 13 hours. 4) No patient had respiratory depression, itching or vomiting but some patients had urinary retention and nausea. In conclusion, the present study suggests that pentazocine is a useful agent for postope-ratilve pain relief when injected epidurally.
Analgesia ; Hate ; Humans ; Injections, Epidural ; Narcotics ; Nausea ; Pain, Postoperative* ; Pentazocine* ; Pruritus ; Respiratory Insufficiency ; Solubility ; Urinary Retention ; Vomiting

We have already reported good effect of meperidin and pentazocin as the sole agent for spinal anesthesia. The present study was undertaken to examine toxic effects of pentazocin and meperidine on peripheral nerve tissue. 11 rats were divided into three groups i.e. pentazocine, meperidine and control group. The sciatic nerves of adult rats were exposed and injected with pentazocin 0.5ml(15mg) or meperidine 0.5ml (25mg). Two specimens of normal nerve and another two specimens injected with normal saline 0.5 ml were used as the controIs. The nerve was examined under electron microcopy at 24 hours, 48 hours, 1 week and 4 weeks after the injection of each of the drugs. A total of twenty injections were carried out in 11 rats. The results were as follows: The pentazocien group revealed hydropic changes in the mitochondria and ER of axon and Schwann cell but the degree of injury was not significant and was reversible. The meperidine group showed hydropic changes that were not significant but the specimen taken at one week revealed severe axonal and myeline changes, admixed with fat globules and Schwann cell with severe fatty changes in the cytoplasm. Although most of the above mentioned changes may reverse, it is not certain yet that pentazocin and meperidine are free of toxicity on nerve cells until further study is done to find the causes of the severe histolgical changes which were shown in the one week specimen with demerol.
Adult ; Anesthesia, Spinal ; Animals ; Axons ; Cytoplasm ; Humans ; Meperidine ; Mitochondria ; Myelin Sheath ; Narcotics* ; Neurons ; Pentazocine ; Peripheral Nerves* ; Rats* ; Sciatic Nerve

From April 1974, we have performed modified neurcleptanesthesia with diazepam-pentazocine N2O in 60 cases. These patients were given diazepam, 0.3 mg/kg, and pentazocine, 1 0 mg/kg, intravenously. Endotracheal intubation was performed in all cases after a sleep dose of thiopental or N2O by mask, with an adequate dose of succinylcholine. Anesthesia was maintained with N2O-O2, suplemented with muscle relaxants. During the operation, we gave an additional dose of diazepam or pentazocine, if needed. The results were as follows: Respiratory depression was observed after the administration of diazepam and pentazocine, but this depression disappeared in the early postoperative recovery period. 2. Recovery from anesthesia was rapid and smocth. Almost all patients awakened within 5 minutes after discontinuance of N2O admir.istration. 3. Analgesia and sedation extended well into the postoperative period, minimizing the need for narcotics. 4 Postoperative nausea and vomiting appeared in only 7% of cases. 5 Circulagory stability was marked during and after operation, being particulary valuable in the elderly and poor risk patients.
Aged ; Analgesia ; Anesthesia ; Depression ; Diazepam ; Humans ; Intubation, Intratracheal ; Masks ; Narcotics ; Pentazocine ; Postoperative Nausea and Vomiting ; Postoperative Period ; Respiratory Insufficiency ; Succinylcholine ; Thiopental

In relief of postoperative pain, the value of epidural or subdural injection of opioids including morphine, methadone, petidine and fentanyl is now well established. The advantages of epidural or subdural over parenteral opioids is prolonged duration of analgesia, which last from several hours to several days, without sympathetic and motor blockade. But undesirable side effects include pruritus, urinary retention, delayed onset of somnolence, and cardiovascular and respiratory depression. To reduce postoperative pain, we evaluated the effects of caudal pentazocine 0.2-0.4 mg/kg with lidocaine 1.5% 400 mg for perianal surgery in 36 cases. The results were as follows: 1) There was no difference in analgesic onset between the Control Group (used lidocaine only) and Group A and B (mixed use of lidocaine and pentazocine: Group A, 0.2 mg/kg pentazocine; Group B, 0.4 mg/kg) 2) Mean duration of analgesia following caudal pentazocine and lidocaine injection was over 12 hours, but was less than 5 hours in the used lidocaine only. 3) Urinary retention was observed in all groups; 3 case in the Control group, and 4 cases in Group A and B. 4) In Group A and B, 6 cases had not used analgesics within 24 hours after caudal anesthesia. 5) No specific clinical changes were noted in the vital signs in all groups.
Analgesia ; Analgesics ; Analgesics, Opioid ; Anesthesia, Caudal ; Fentanyl ; Lidocaine ; Methadone ; Morphine ; Pain, Postoperative ; Pentazocine* ; Pruritus ; Respiratory Insufficiency ; Urinary Retention ; Vital Signs

The authors have already reported good local anesthetic effects of meperidine and pentazocine clinically in patients scheduled for various surgeries, followed by experimental evaluation of toxic effects of two drugs on the sciatic nerve of rats. Intraspinal (spinal, epidural) morphine as well as other narcotics administration has been widely used and well established for pain control. The action mechanism of intraspinal narcotics has been well defined, and meperidine and Pentazocine have been reported to be used as a sole agent for spinal anesthesia. We assurned that the action mechanism of subarachoid meperidine or pentazocine might be different to some extent from that of morphine. This investigation was primarily undertaken to examine the difference in action between meperidine and morphine and also to evaluate neurotoxic effects on sciatic nerve of dogs. Adult Korean dogs were chosen as exoerunebtak abunaks because it is easy to observe physiologic activity with responses and to avoid of manipulating trauma. The dogs were intubated and anesthetised with halothane and nitrous oxide. The sciatic nerve of the dogs was exposed and stimulated by a nerve stimulator to observe myoneural response and then injectied with 1% morphine 0.5 mg (Group 1), 5% meperidine 25 mg (Group 2) and 3% pentazocine 15 mg (Group 3). The dog was carefully observed in recovery room to see the myoneural activity After 1 week, 1 month or 2 months of careful observation, a specimen was taken under reanesthesia at 1 week, 1 month and 2 months after the careful obaervation, When the sciatic nerve was stimulated by a nerve stimulator, the normal muscle twitch was observed clearly in Group 1 with themorphine injection but was not observed in Group 2 with meperidine and Group 3 with pentazocine injection. Complete motor paralysis was noticed in Group 2 and 3 during the recovery period which lasted about 90 minutes, almost the same as the duration of drugs for spinal anesthesia, No complications were noticed in the 3 group during the periods of one week one month and two months. All specimens were examined and no abnormal findings were observed in the 3 groups. All specimens of the 3 groups were investigated under electrom microscopic examination and they revealed mild vacuolizations scattered in axon and ummyelinated nerves on the only some of the specimens and these were not significant. Severe nerve damage which was seen in the meperidine group of a preliminary experiment was not observed in this study. As a result of this investigation, we have not observed significant toxic effects microscopically or fuctioually.
Adult ; Anesthesia, Spinal ; Anesthetics ; Animals ; Axons ; Dogs* ; Halothane ; Humans ; Meperidine* ; Morphine* ; Narcotics ; Nitrous Oxide ; Paralysis ; Pentazocine* ; Peripheral Nerves ; Rats ; Recovery Room ; Sciatic Nerve*