JPH0138086B2 - - Google Patents
Info
- Publication number
- JPH0138086B2 JPH0138086B2 JP56108815A JP10881581A JPH0138086B2 JP H0138086 B2 JPH0138086 B2 JP H0138086B2 JP 56108815 A JP56108815 A JP 56108815A JP 10881581 A JP10881581 A JP 10881581A JP H0138086 B2 JPH0138086 B2 JP H0138086B2
- Authority
- JP
- Japan
- Prior art keywords
- pindolol
- sedative
- administration
- hypnotic
- therapeutic agent
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- PHUTUTUABXHXLW-UHFFFAOYSA-N pindolol Chemical compound CC(C)NCC(O)COC1=CC=CC2=NC=C[C]12 PHUTUTUABXHXLW-UHFFFAOYSA-N 0.000 claims description 25
- 229960002508 pindolol Drugs 0.000 claims description 24
- 230000004799 sedative–hypnotic effect Effects 0.000 claims description 12
- 239000003814 drug Substances 0.000 claims description 11
- 229940124597 therapeutic agent Drugs 0.000 claims description 9
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 claims description 8
- 206010012335 Dependence Diseases 0.000 claims description 7
- 208000007848 Alcoholism Diseases 0.000 claims description 6
- 201000007930 alcohol dependence Diseases 0.000 claims description 6
- 239000004480 active ingredient Substances 0.000 claims description 3
- 229940125717 barbiturate Drugs 0.000 claims description 3
- 239000003204 tranquilizing agent Substances 0.000 claims description 2
- 230000002936 tranquilizing effect Effects 0.000 claims description 2
- 150000001298 alcohols Chemical class 0.000 claims 1
- FTOAOBMCPZCFFF-UHFFFAOYSA-N 5,5-diethylbarbituric acid Chemical compound CCC1(CC)C(=O)NC(=O)NC1=O FTOAOBMCPZCFFF-UHFFFAOYSA-N 0.000 description 10
- IGLYMJRIWWIQQE-QUOODJBBSA-N (1S,2R)-2-phenylcyclopropan-1-amine (1R,2S)-2-phenylcyclopropan-1-amine Chemical compound N[C@H]1C[C@@H]1C1=CC=CC=C1.N[C@@H]1C[C@H]1C1=CC=CC=C1 IGLYMJRIWWIQQE-QUOODJBBSA-N 0.000 description 9
- AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical compound C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 description 9
- 229960003741 tranylcypromine Drugs 0.000 description 9
- AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 description 8
- 229960003529 diazepam Drugs 0.000 description 8
- 229960002319 barbital Drugs 0.000 description 5
- 208000034308 Grand mal convulsion Diseases 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- 229960003712 propranolol Drugs 0.000 description 4
- 206010010904 Convulsion Diseases 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- 230000003288 anthiarrhythmic effect Effects 0.000 description 3
- 230000036461 convulsion Effects 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 206010002091 Anaesthesia Diseases 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- GQPLMRYTRLFLPF-UHFFFAOYSA-N Nitrous Oxide Chemical compound [O-][N+]#N GQPLMRYTRLFLPF-UHFFFAOYSA-N 0.000 description 2
- 208000037048 Prodromal Symptoms Diseases 0.000 description 2
- 230000037005 anaesthesia Effects 0.000 description 2
- 230000003276 anti-hypertensive effect Effects 0.000 description 2
- HNYOPLTXPVRDBG-UHFFFAOYSA-N barbituric acid Chemical compound O=C1CC(=O)NC(=O)N1 HNYOPLTXPVRDBG-UHFFFAOYSA-N 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 235000010980 cellulose Nutrition 0.000 description 2
- 230000002920 convulsive effect Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- KJONHKAYOJNZEC-UHFFFAOYSA-N nitrazepam Chemical compound C12=CC([N+](=O)[O-])=CC=C2NC(=O)CN=C1C1=CC=CC=C1 KJONHKAYOJNZEC-UHFFFAOYSA-N 0.000 description 2
- 229960001454 nitrazepam Drugs 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 235000012222 talc Nutrition 0.000 description 2
- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 description 1
- 229930182837 (R)-adrenaline Natural products 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 206010013752 Drug withdrawal convulsions Diseases 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 206010060891 General symptom Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 206010022998 Irritability Diseases 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 206010028347 Muscle twitching Diseases 0.000 description 1
- 206010052904 Musculoskeletal stiffness Diseases 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 206010043994 Tonic convulsion Diseases 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 230000001773 anti-convulsant effect Effects 0.000 description 1
- 229940030600 antihypertensive agent Drugs 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 230000003126 arrythmogenic effect Effects 0.000 description 1
- 230000004872 arterial blood pressure Effects 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 229940053197 benzodiazepine derivative antiepileptics Drugs 0.000 description 1
- 150000001557 benzodiazepines Chemical class 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 230000004531 blood pressure lowering effect Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 235000001465 calcium Nutrition 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 210000000748 cardiovascular system Anatomy 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 206010013663 drug dependence Diseases 0.000 description 1
- 229960005139 epinephrine Drugs 0.000 description 1
- 210000003194 forelimb Anatomy 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000001727 glucose Nutrition 0.000 description 1
- 239000003326 hypnotic agent Substances 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000035987 intoxication Effects 0.000 description 1
- 231100000566 intoxication Toxicity 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Substances [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 230000004973 motor coordination Effects 0.000 description 1
- TZBAVQKIEKDGFH-UHFFFAOYSA-N n-[2-(diethylamino)ethyl]-1-benzothiophene-2-carboxamide;hydrochloride Chemical compound [Cl-].C1=CC=C2SC(C(=O)NCC[NH+](CC)CC)=CC2=C1 TZBAVQKIEKDGFH-UHFFFAOYSA-N 0.000 description 1
- 235000013842 nitrous oxide Nutrition 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 229940032164 pindolol 15 mg Drugs 0.000 description 1
- 230000000216 proconvulsive effect Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 235000015424 sodium Nutrition 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 208000011117 substance-related disease Diseases 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 229940125725 tranquilizer Drugs 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
Description
本発明は活性成分としてピンドロールを含んで
なるアルコール中毒または鎮静催眠薬中毒治療剤
に関する。
従来、アルコール類、バルビツレート類及びト
ランキライザー退薬症候の治療にはベンゾジアゼ
ピン誘導体、すなわち、ジアゼパム（DZP）及
びニトラゼパム（NZP）が広汎に用いられてい
る。しかしながら、ジアゼパムはこれら鎮静催眠
薬に対して交叉耐性及び交叉依存性があるため、
前記鎮静催眠薬による中毒が回復した後にジアゼ
パム退薬による禁断症候が発現する。そればかり
でなく、中毒患者退院後にジアゼパム嗜好性が高
まり、乱用の傾向が現われる。
従つて、本発明の目的は前述のような欠点を有
さない鎮静催眠薬治療剤を提供することにある。
本発明者らは、交叉耐性及び交叉依存性を有さな
い鎮静催眠薬中毒治療剤を開発すべく鋭意検討を
重ねた結果、従来高血圧・不整脈用剤として臨床
的に用いられているβ−遮断薬ピンドロールが意
外にもバルビタール退薬痙れん、いらだち、全身
の筋硬直、運動協調障害等の鎮静催眠薬退薬症候
を抑制でき、しかも薬物依存性ならびにジアゼパ
ムに見られるような交叉耐性及び交叉依存性を示
さないことを見い出した。
ピンドロールの鎮静催眠薬退薬症候に対する作
用を薬理試験により検討した。試験は、バルビタ
ール退薬時にモノアミン酸化阻害薬トラニルサイ
プロミン（Tcp）を適用することによつて誘発さ
れる痙れん前駆症候及び間代性−強直性痙れんに
対するピンドロールの抑制作用を測定することに
より行なつた「田頭栄治郎ら：第54回日本薬理学
会総会要旨集（福岡）、120ページ（1981年）参
照〕。
田頭らの方法〔田頭栄治郎ら：
Psychopharmacology、57、137〜144ページ
（1978年）〕に従つて、恒温恒湿下において飼育管
理されたスプラグ−ドーリー〔Sprague−
Dawley）系雄ラツト（体重100〜120ｇ）に、次
のような飼料を順次与えることにより、パルビタ
ール依存を獲得させた：バルビタール(B)0.5及び
１mg／ｇ混入飼料を４日間、B1及び２mg／ｇ混
入飼料を６日間、B2及び４mg／ｇ混入飼料を６
日間、B4及び６mg／ｇ混入飼料を10日間、なら
びにB6及び８mg／ｇ混入飼料を10日間。バルビ
タール最終適用後、バルビタール混入飼料を普通
飼料に置き換え、退薬48時間目（重症の退薬症候
の発現が持続している時点）に、各群５〜６匹か
ら成る５群のラツトに、ピンドロール単独（３
mg／Kgもしくは10mg／Kg、腹腔内投与）またはピ
ンドロール（３mg／Kgもしくは10mg／Kg、腹腔内
投与）とジアゼパム（５mg／Kg、経口投与）との
組み合わせを投与した。対照群にはピンドロール
を投与せず、代わりに生理食塩水を腹腔内投与し
た。各薬物投与の30分後にトラニルサイプロミン
20mg／Kgを腹腔内投与した。次いで、トラニルサ
イプロミンを投与してから痙れんの前駆症候（カ
ンガル−様姿勢あるいは前肢のれん縮）が発現さ
れるまでの時間（T1）、ならびにトラニルサイプ
ロミンを投与してから間代性一強直性痙れんが発
現されるまでの時間（T2）を測定した。トラニ
ルサイプロミン投与後30分後、一般症候を観察
し、６時間以内のTcp誘発痙れんによる死亡率を
算出した。得られた結果を次の第１表に示す。
The present invention relates to a therapeutic agent for alcoholism or sedative-hypnotic addiction comprising pindolol as an active ingredient. Traditionally, benzodiazepine derivatives, namely diazepam (DZP) and nitrazepam (NZP), have been widely used to treat alcohol, barbiturate and tranquilizer withdrawal symptoms. However, diazepam is cross-resistant and cross-dependent to these sedative-hypnotics;
After recovery from intoxication caused by the sedative-hypnotic drug, withdrawal symptoms occur due to diazepam withdrawal. Moreover, after addicted patients are discharged from the hospital, their preference for diazepam increases and their tendency to abuse appears. It is therefore an object of the present invention to provide a sedative-hypnotic therapeutic agent that does not have the disadvantages mentioned above.
The present inventors have conducted intensive studies to develop a treatment for sedative-hypnotic addiction that does not have cross-tolerance and cross-dependence. The drug pindolol is surprisingly able to suppress sedative-hypnotic withdrawal symptoms such as barbital withdrawal convulsions, irritability, general muscle stiffness, and impaired motor coordination, and also prevents drug dependence as well as cross-tolerance and cross-dependence seen with diazepam. I discovered that it does not show any gender. The effects of pindolol on sedative-hypnotic withdrawal symptoms were investigated through pharmacological tests. The study measured the inhibitory effects of pindolol on proconvulsive symptoms and clonic-tonic convulsions induced by the application of the monoamine oxidation inhibitor tranylcypromine (Tcp) during barbital withdrawal. The method of Tagashira et al. [Eijiro Tagashira et al.
Psychopharmacology, 57 , pp. 137-144 (1978)].
Male Dawley rats (body weight 100-120 g) were made to become dependent on parbital by sequentially feeding them the following diets: Feed containing barbital (B) 0.5 and 1 mg/g for 4 days; g mixed feed for 6 days, and B2 and 4 mg/g mixed feed for 6 days.
B4 and 6 mg/g mixed feed for 10 days, and B6 and 8 mg/g mixed feed for 10 days. After the final application of barbital, the barbital-containing feed was replaced with normal feed, and 48 hours after drug withdrawal (when severe withdrawal symptoms persisted), 5 groups of 5 to 6 rats in each group were treated. Pindolol alone (3
mg/Kg or 10 mg/Kg ip) or a combination of pindolol (3 mg/Kg or 10 mg/Kg ip) and diazepam (5 mg/Kg orally). The control group did not receive pindolol, but instead received physiological saline intraperitoneally. Tranylcypromine 30 minutes after each drug administration
20 mg/Kg was administered intraperitoneally. Next, we measured the time (T 1 ) from the administration of tranylcypromine to the onset of convulsive prodromal symptoms (kangal-like posture or forelimb twitching), as well as the time from administration of tranylcypromine to the onset of convulsive prodromal symptoms (T 1 ). The time until onset of tonic convulsions (T 2 ) was measured. Thirty minutes after administration of tranylcypromine, general symptoms were observed, and the mortality rate due to Tcp-induced convulsions within 6 hours was calculated. The results obtained are shown in Table 1 below.
【表】
前記第１表に示されるように、対照群にトラニ
ルサイプロミン20mg／Kgを投与すると投与後８〜
９分に80〜100％のほとんど全例に重症の間代性
−強直性痙れんが発現した。一方、ピンドロール
３mg／Kg及び10mg／Kgを前処置するとトラニルサ
イプロミン誘発痙れんの強度は著しく軽減され、
痙れんの発現率も著しく抑制され（抑制率は各々
67％及び83％）、ピンドロールの用量に相関した
間代性−強直性痙れん抑制効果がみれた。トラニ
ルサイプロミン投与後６時間以内の死亡率も有意
に軽減された〔ピンドロール無投与の場合：80
％、ピンドロールの場合：０〜17％〕。さらに、
ピンドロールにジアゼパム少量を併用すると、痙
れん抑制作用は増強され（間代性一強直性痙れん
の発現は完全に抑制された）、トラニルサイプロ
ミン投与後６時間以内の死亡率は０％であつた。
第１表から、ピンドロールが著しく優れたバルビ
ツレート退薬症候治療効果を有することがわか
る。
比較のため、以下に従来知られているピンドロ
ールの薬理作用、すなわち、降圧作用及び抗不整
脈作用についての薬理データを記載する。
降圧作用について
ピンドロール15mg／日を本態性高血圧症患者15
例に８週間にわたり経口投与し、降圧剤としての
有用性を確認した。その降圧効果は２週後に有意
であり、以後８週目まで安定した降圧を示した。
脈拍数は６週以後有意な低下を示したが、その程
度は軽微であつた。（「薬理と治療」、Vol.8、No.
３、207〜210ページ、1980年３月号参照）。
抗不整脈作用について
雑種成犬20頭にフローセン、笑気、酸素麻酔
下、ピンドロール0.02mg／Kgを静脈注射した。ピ
ンドロールの投与により、心拍数は６〜９％と軽
度の減少を示し（プロプラノロールで16〜22％；
両者の間に有意差あり）、動脈圧の変化はピンド
ロールで１〜２％とやや減少の傾向を示したが総
体的に有意な変化とは認められず（プロプラノロ
ールでは１〜５％）、そして心拍出量は９〜11％
と軽度の減少を示した（プロプラノロールで14〜
24％：両者の間に有意差あり）。不整脈誘発エピ
ネフイリン量はピンドロール投与群では平均14μ
ｇ／Kg、プロプラノロール投与群では平均15μ
ｇ／Kgであつた。これらの結果から、ピンドロー
ル0.02mg／Kgとプロプラノロール0.1mg／Kgとは
同程度の抗不整脈作用を示すが心循環系に対する
抑制度はピンドロールの方がはるかに軽度であつ
た。（「麻酔」、第巻、第10号、1134〜1135ペ
ージ参照）。
ピンドロールのLD50（mg／Kg）は次のとおりで
ある：マウスに対する経口投与の場合、雄で
253.6、雌で268.7；マウスに対する静脈内投与の
場合、雄で35.7、雌で38.8；ラツトに対する経口
投与の場合、雄で263.3、雌で269.6；ラツトに対
する静脈内投与の場合、雄で53.6、雌で51.3であ
る。
本発明によれば、活性成分としてピンドロール
を含む、アルコール中毒または鎮静催眠薬中毒治
療剤が提供される。本発明に係る治療剤は錠剤、
注射剤として調製でき、経口的にまたは皮下注射
もしくは静脈注射により投与できる。
本発明に係る治療剤に用いることのできる担体
としては、経口投与のための錠剤の場合、乳糖、
デンプン、白糖、ブドウ糖、結晶セルロース、炭
酸カルシウムもしくはカオリンのような賦形剤；
デンプン、ゼラチンもしくはヒドロキシプロピル
セルロースのような結合剤；デンプン、寒天、ゼ
ラチン、カルボキシメチルセルロースナトリウム
もしくはカルシウムまたは結晶セルロースのよう
な崩壊剤、ならびに；ステアリン酸マグネシウム
もしくはカルシウム、タルク、マクロゴール4000
もしくは6000、ステアリン酸のような滑沢剤を挙
げることができる。
本発明に係る治療剤は製薬業界における常法に
従つて調製できる。
本発明に係るアルコール中毒または鎮静催眠薬
中毒治療剤のヒトに対する日用量（経口投与）
は、ピンドロールとして約30mgである。
本発明のアルコール中毒または鎮静催眠薬中毒
治療剤（錠剤）の一処方例を次にあげる。錠剤１
錠中の組成：
ピンドロール 5.0mg
結晶セルロース 90.0mg
乳糖 20.7mg
ヒドロキシプロピルセルロース 0.6mg
タルク 3.7mg
全量120.0mg。[Table] As shown in Table 1 above, when 20 mg/Kg of tranylcypromine was administered to the control group, the
Severe clonic-tonic convulsions developed in almost all cases (80-100%) at 9 minutes. On the other hand, pretreatment with pindolol 3 mg/Kg and 10 mg/Kg significantly reduced the intensity of tranylcypromine-induced convulsions;
The incidence of convulsions was also significantly suppressed (the suppression rate was
(67% and 83%), and a dose-related effect of pindolol on suppressing clonic-tonic convulsions was observed. The mortality rate within 6 hours after administration of tranylcypromine was also significantly reduced [without pindolol administration: 80
%, for pindolol: 0-17%]. moreover,
When pindolol was combined with a small amount of diazepam, the anticonvulsant effect was enhanced (the onset of clonic tonic convulsions was completely suppressed), and the mortality rate within 6 hours after administration of tranylcypromine was 0%. It was hot.
From Table 1, it can be seen that pindolol has an extremely excellent therapeutic effect on barbiturate withdrawal symptoms. For comparison, pharmacological data regarding the conventionally known pharmacological effects of pindolol, ie, antihypertensive and antiarrhythmic effects, are described below. About antihypertensive effect: Pindolol 15mg/day for patients with essential hypertension15
The drug was orally administered to animals for 8 weeks, and its usefulness as an antihypertensive agent was confirmed. The blood pressure lowering effect was significant after 2 weeks, and stable blood pressure reduction was shown until 8 weeks thereafter.
Although the pulse rate showed a significant decrease after 6 weeks, the degree of decrease was slight. (“Pharmacology and Treatment”, Vol.8, No.
3, pp. 207-210, March 1980 issue). Regarding antiarrhythmic effects Pindolol 0.02 mg/Kg was intravenously injected into 20 adult mongrel dogs under Frocene, laughing gas, and oxygen anesthesia. Administration of pindolol showed a mild decrease in heart rate of 6-9% (16-22% with propranolol;
Although there was a significant difference between the two), the change in arterial pressure showed a slight tendency to decrease by 1-2% with pindolol, but no significant change was observed overall (1-5% with propranolol), and Cardiac output is 9-11%
and showed a mild decrease (14~ with propranolol).
24%: There is a significant difference between the two). The arrhythmogenic epinephrine dose averaged 14μ in the pindolol group.
g/Kg, average 15μ in propranolol group
g/Kg. From these results, pindolol 0.02 mg/Kg and propranolol 0.1 mg/Kg showed similar antiarrhythmic effects, but pindolol had a much milder degree of inhibition on the cardiovascular system. (See Anesthesia, Vol. No. 10, pp. 1134-1135). The LD 50 (mg/Kg) of pindolol is: For oral administration to mice, the LD 50 (mg/Kg) is:
253.6, 268.7 in females; intravenous administration in mice, 35.7 in males, 38.8 in females; oral administration in rats, 263.3 in males, 269.6 in females; intravenous administration in rats, 53.6 in males, females It is 51.3. According to the present invention, there is provided a therapeutic agent for alcoholism or sedative-hypnotic addiction, which contains pindolol as an active ingredient. The therapeutic agent according to the present invention is a tablet,
It can be prepared as an injection and administered orally or by subcutaneous or intravenous injection. In the case of tablets for oral administration, carriers that can be used in the therapeutic agent according to the present invention include lactose,
Excipients such as starch, white sugar, glucose, microcrystalline cellulose, calcium carbonate or kaolin;
Binders such as starch, gelatin or hydroxypropyl cellulose; disintegrants such as starch, agar, gelatin, sodium or calcium carboxymethylcellulose or crystalline cellulose, and; magnesium or calcium stearate, talc, macrogol 4000
or 6000, lubricants such as stearic acid. The therapeutic agent according to the present invention can be prepared according to conventional methods in the pharmaceutical industry. Daily dose for humans of the therapeutic agent for alcoholism or sedative-hypnotic addiction according to the present invention (oral administration)
is approximately 30 mg as pindolol. An example of the formulation of the treatment agent (tablet) for alcoholism or sedative-hypnotic addiction of the present invention is given below. tablet 1
Composition in the tablet: Pindolol 5.0mg Crystalline cellulose 90.0mg Lactose 20.7mg Hydroxypropylcellulose 0.6mg Talc 3.7mg Total amount 120.0mg.
Claims (1)
ルコール中毒または鎮静催眠薬中毒治療剤。 ２ アルコール類、バルビツレート類またはトラ
ンキライザーの禁断症状を治療するのに用いる特
許請求の範囲第１項記載のアルコール中毒または
鎮静催眠薬中毒治療剤。[Scope of Claims] 1. A therapeutic agent for alcoholism or sedative-hypnotic addiction, comprising pindolol as an active ingredient. 2. The therapeutic agent for alcoholism or sedative-hypnotic addiction according to claim 1, which is used to treat withdrawal symptoms of alcohols, barbiturates, or tranquilizers.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP56108815A JPS5810518A (en) | 1981-07-14 | 1981-07-14 | Remedy for alcoholism or sedative and hypnotic addiction |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP56108815A JPS5810518A (en) | 1981-07-14 | 1981-07-14 | Remedy for alcoholism or sedative and hypnotic addiction |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5810518A JPS5810518A (en) | 1983-01-21 |
| JPH0138086B2 true JPH0138086B2 (en) | 1989-08-11 |
Family
ID=14494201
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP56108815A Granted JPS5810518A (en) | 1981-07-14 | 1981-07-14 | Remedy for alcoholism or sedative and hypnotic addiction |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS5810518A (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2630396B2 (en) * | 1987-04-30 | 1997-07-16 | 三菱レイヨン株式会社 | Doctor knife blade |
| US8134029B2 (en) | 2002-09-16 | 2012-03-13 | Sunovion Pharmaceuticals Inc. | Treatment of CNS disorders with trans 4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-napthalenamine |
| JP2012526832A (en) * | 2009-05-13 | 2012-11-01 | スノビオン プハルマセウトイカルス インコーポレイテッド | Composition comprising transnorsertraline and serotonin receptor 1A agonist / antagonist and use thereof |
-
1981
- 1981-07-14 JP JP56108815A patent/JPS5810518A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5810518A (en) | 1983-01-21 |
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